244 results on '"Naihe Jing"'
Search Results
102. A 3D Atlas of Hematopoietic Stem and Progenitor Cell Expansion by Multi-dimensional RNA-Seq Analysis
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Feng Liu, Denghui Liu, Guangdun Peng, Yifan Zhang, Naihe Jing, Daosheng Ai, Yanyan Ding, Chunyu Zhou, Peng Lv, Suwei Gao, Xingwei Chen, Guizhong Cui, Jing-Dong J. Han, Yuanyuan Xue, Xiaohan Wang, Shengbao Suo, and Yizhou Li
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0301 basic medicine ,genetic processes ,RNA-Seq ,General Biochemistry, Genetics and Molecular Biology ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,Animals ,natural sciences ,Stem Cell Niche ,Progenitor cell ,lcsh:QH301-705.5 ,Zebrafish ,biology ,Hematopoietic Tissue ,Cell cycle ,Hematopoietic Stem Cells ,biology.organism_classification ,Hematopoiesis ,Cell biology ,Gene expression profiling ,Haematopoiesis ,030104 developmental biology ,lcsh:Biology (General) ,Single-Cell Analysis ,030217 neurology & neurosurgery ,Signal Transduction - Abstract
Summary: In vertebrates, hematopoiesis occurring in different niches is orchestrated by intrinsic and extrinsic regulators. Previous studies have revealed numerous linear and planar regulatory mechanisms. However, a multi-dimensional transcriptomic atlas of any given hematopoietic organ has not yet been established. Here, we use multiple RNA sequencing (RNA-seq) approaches, including cell type-specific, temporal bulk RNA-seq, in vivo GEO-seq, and single-cell RNA-seq (scRNA-seq), to characterize the detailed spatiotemporal transcriptome during hematopoietic stem and progenitor cell (HSPC) expansion in the caudal hematopoietic tissue (CHT) of zebrafish. Combinatorial expression profiling reveals that, in the CHT niche, HSPCs and their neighboring supporting cells are co-regulated by shared signaling pathways and intrinsic factors, such as integrin signaling and Smchd1. Moreover, scRNA-seq analysis unveils the strong association between cell cycle status and HSPC differentiation. Taken together, we report a global transcriptome landscape that provides valuable insights and a rich resource to understand HSPC expansion in an intact vertebrate hematopoietic organ. : In this work, Xue et al. establish a 3D atlas of zebrafish caudal hematopoietic tissue and reveal mechanisms underlying HSPC expansion in an intact hematopoietic organ by multi-dimensional RNA-seq. Keywords: hematopoietic stem and progenitor cell, multi-dimensional RNA-seq, 3D atlas, signaling, zebrafish
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- 2019
103. Author Correction: Lung regeneration by multipotent stem cells residing at the bronchioalveolar-duct junction
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Wenjuan Pu, Libo Zhang, Dongqing Cai, Yi Arial Zeng, Guangdun Peng, Naihe Jing, Huan Zhao, Tao Ren, Yan Li, Xueying Tian, Muxue Tang, Guizhong Cui, Xiuzhen Huang, Yu Nie, Lingjuan He, Wenke Guo, Wei Yu, Kuo Liu, Zhen Qin, Bin Zhou, Qiaozhen Liu, Shengshou Hu, Zengyong Qiao, Hongbin Ji, He-Feng Huang, Shun Yao, and Rui Yang
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Pathology ,medicine.medical_specialty ,medicine.anatomical_structure ,Lung ,Multipotent Stem Cell ,Regeneration (biology) ,Genetics ,medicine ,Biology ,Duct (anatomy) - Abstract
In the version of this article initially published, the following grant numbers and recipients were missing from the Acknowledgements: XDB19000000 to H.J. and B.Z.; 81430066 and 31621003 to H.J.; 2017YFA0505500 to H.J.; and 15XD1504000 to H.J. The errors have been corrected in the HTML and PDF versions of the article.
- Published
- 2019
104. Author Correction: Hormones induce the formation of luminal-derived basal cells in the mammary gland
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Tom H. Cheung, Wenqian Song, Qi Yin, Jingsong Li, Guangdun Peng, JianFeng Chen, Weimin Jiang, Qing Cissy Yu, Yi Arial Zeng, Naihe Jing, Ran Wang, and Ruikai Yang
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medicine.medical_specialty ,Mammary gland ,Mice, Nude ,Breast Neoplasms ,Biology ,Mice ,Basal (phylogenetics) ,Mammary Glands, Animal ,Pregnancy ,Internal medicine ,Correct name ,medicine ,Animals ,Cell Lineage ,Wnt Signaling Pathway ,Molecular Biology ,Progesterone ,beta Catenin ,Gene Expression Profiling ,Stem Cells ,Transdifferentiation ,Estrogen Receptor alpha ,Correction ,Cell Differentiation ,Epithelial Cells ,Estrogens ,Cell Biology ,Wnt Proteins ,Endocrinology ,medicine.anatomical_structure ,Female ,Stem cell ,Author name ,Hormone - Abstract
In the mammary gland, it is widely believed that the luminal cells are unipotent after birth, contributing only to the luminal compartment in normal development. Here, by lineage tracing, we uncovered an unexpected potential of luminal cells that can give rise to basal cells during pregnancy. These luminal-derived basal cells (LdBCs) persisted through mammary regression and generated more progeny in successive rounds of pregnancies. LdBCs express basal markers as well as estrogen receptor α (ERα). In ovariectomized (OVX) mice, stimulation with estrogen and progesterone promoted the formation of LdBCs. In serial transplantation assays, LdBCs were able to reconstitute new mammary glands in a hormone-dependent manner. Transcriptome analysis and genetic experiments suggest that Wnt/β-catenin signaling is essential for the formation and maintenance of LdBCs. Our data uncover an unexpected bi-potency of luminal cells in a physiological context. The discovery of ERα
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- 2019
105. Base-Editing-Mediated R17H Substitution in Histone H3 Reveals Methylation-Dependent Regulation of Yap Signaling and Early Mouse Embryo Development
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Naihe Jing, Xingxu Huang, Yunbo Qiao, Yajing Liu, Shisheng Huang, Ran Wang, Yu Wei, Jianan Li, Changyang Zhou, Guang Yang, Zongyang Lu, Xiajun Li, Xianfa Yang, Wenqin Ying, and Hui Yang
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0301 basic medicine ,Protein-Arginine N-Methyltransferases ,CARM1 ,Mutation, Missense ,Embryonic Development ,Cell Cycle Proteins ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Histones ,Mice ,03 medical and health sciences ,Histone H3 ,Transactivation ,0302 clinical medicine ,Catalytic Domain ,Cell Line, Tumor ,Histone methylation ,Animals ,lcsh:QH301-705.5 ,Adaptor Proteins, Signal Transducing ,YAP1 ,Mice, Inbred ICR ,Cell Cycle ,Gene Expression Regulation, Developmental ,YAP-Signaling Proteins ,Embryo ,Methylation ,Cell biology ,Histone Code ,Mice, Inbred C57BL ,030104 developmental biology ,lcsh:Biology (General) ,DNA methylation ,Transcriptome ,030217 neurology & neurosurgery ,Signal Transduction - Abstract
Summary: The coactivator-associated arginine methyltransferase CARM1 catalyzes the methylation of histone H3 arginine 17/26 (H3R17/26me) and non-histone proteins at arginine residues to regulate gene transactivation through profiling or Carm1 overexpression assays. However, the direct relationship between H3R17/26me and its causal role in mouse embryo development remains largely unclear. Here, we use rAPOBEC1-XTEN-Cas9n-UGI (BE3) to efficiently introduce a point mutation (R17H) at multiple Hist1/2H3 loci and a premature-stop codon into the catalytic domain of CARM1 in mouse embryos, resulting in remarkable downregulation of H3R17me levels and developmental defects in pre-implantation and fetal embryos. Transcriptomic analysis reveals that Yap1 and cell cycle signaling pathways are dysregulated in Carm1 truncation and H3R17H substitution embryos, and Yap1 overexpression could rescue the base-editing-elicited defects. Our data establish the direct regulatory relationship between CARM1-mediated H3R17me and early mouse embryo development and demonstrate that Yap1 acts downstream of CARM1-mediated H3R17me to regulate the mouse embryo development. : Yang et al. apply CRISPR-Cas9-based base editing tools to precisely introduce substitutions at multiple histone H3 loci to disrupt methylation at histone H3 arginine 17 (H3R17me), and they find that CARM1-mediated H3R17me regulates embryo development through Yap1 and cell cycle signaling pathways. Keywords: base editing, H3R17, CARM1, histone methylation, Yap1 signaling, embryo development
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- 2019
106. ZIP-seq: genome-wide mapping of trinucleotide repeats at single-base resolution
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Ronggui Hu, Naihe Jing, Xingxing Xu, Chen Kan, Yuanyuan Li, Xing Fu, Yonghui Tao, Xiaoyan Ding, Kangcheng Ruan, and Tao Yu
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Sequence analysis ,Resolution (electron density) ,Chromosome Mapping ,Zinc Fingers ,Sequence Analysis, DNA ,Cell Biology ,General Medicine ,Computational biology ,Biology ,Base (topology) ,Genome ,chemistry.chemical_compound ,Variable number tandem repeat ,Trinucleotide Repeats ,chemistry ,Tandem repeat ,Genetics ,Direct repeat ,Molecular Biology ,DNA - Published
- 2013
107. Location of transient ectodermal progenitor potential in mouse development
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Fredrik Lanner, Qingqing Zhu, Naihe Jing, Lingyu Li, Chang Liu, Janet Rossant, Lu Song, and Steffen Biechele
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Pluripotent Stem Cells ,animal structures ,Nodal Protein ,Embryonic Development ,Nodal signaling ,Ectoderm ,Bone Morphogenetic Protein 4 ,Germ layer ,Biology ,Histogenesis ,Models, Biological ,Somatopleuric mesenchyme ,Mice ,medicine ,Animals ,Cell Lineage ,Molecular Biology ,Genetics ,Mice, Inbred ICR ,Stem Cells ,Embryogenesis ,Diploblasty ,Gene Expression Regulation, Developmental ,Embryo, Mammalian ,Cell biology ,medicine.anatomical_structure ,Epidermal Cells ,Epiblast ,embryonic structures ,Biomarkers ,Signal Transduction ,Developmental Biology - Abstract
Ectoderm is one of the three classic germ layers in the early mouse embryo, with the capacity to develop into both the central nervous system and epidermis. Because it is a transient phase of development with few molecular markers, the early ectoderm is the least understood germ layer in mouse embryonic development. In this work, we studied the differentiation potential of isolated ectoderm tissue in response to BMP signaling at various developmental stages (E6.5, E7.0 and E7.5), and identified a transient region in the anterior-proximal side of the embryo at E7.0 that possesses the ability to become neural or epidermal ectoderm in response to the absence or presence of BMP4, respectively. Furthermore, we demonstrated that inhibition of Nodal signaling could direct the pluripotent E6.5 epiblast cells towards ectoderm lineages during differentiation in explants in vitro. Our work not only improves our understanding of ectodermal layer development in early embryos, but also provides a framework for regenerative differentiation towards ectodermal tissues.
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- 2013
108. Author Correction: Sequential formation and resolution of multiple rosettes drive embryo remodelling after implantation
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Guizhong Cui, Ran Wang, Christos Kyprianou, Naihe Jing, Magdalena Zernicka-Goetz, Antonia Weberling, Neophytos Christodoulou, and Guangdun Peng
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0301 basic medicine ,03 medical and health sciences ,030104 developmental biology ,Computer science ,Published Erratum ,Resolution (electron density) ,Cell Biology ,Computational biology ,Cell biology - Abstract
In the version of this Article originally published, the first name of author Guangdun Peng was spelled incorrectly as Guangdum. This has now been amended in all versions of the Article.
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- 2018
109. The Zinc Finger Transcription Factor Ovol2 Acts Downstream of the Bone Morphogenetic Protein Pathway to Regulate the Cell Fate Decision between Neuroectoderm and Mesendoderm*
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Lingyu Li, Ting Zhang, Yunbo Qiao, Qingqing Zhu, Naihe Jing, Zhihui Xie, and Yongfeng Chen
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Mesoderm ,animal structures ,Cellular differentiation ,Smad Proteins ,Bone Morphogenetic Protein 4 ,Chick Embryo ,Cell fate determination ,Biology ,Bone morphogenetic protein ,Biochemistry ,Avian Proteins ,Mice ,medicine ,Animals ,Humans ,Molecular Biology ,Neural cell ,Neural Plate ,Neuroectoderm ,SOXB1 Transcription Factors ,Endoderm ,Gene Expression Regulation, Developmental ,Cell Differentiation ,Cell Biology ,Embryo, Mammalian ,Molecular biology ,Cell biology ,medicine.anatomical_structure ,Bone morphogenetic protein 4 ,Gene Knockdown Techniques ,embryonic structures ,Chickens ,Neural plate ,Signal Transduction ,Transcription Factors - Abstract
During early embryonic development, bone morphogenetic protein (BMP) signaling is essential for neural/non-neural cell fate decisions. BMP signaling inhibits precocious neural differentiation and allows for proper differentiation of mesoderm, endoderm, and epidermis. However, the mechanisms underlying the BMP pathway-mediated cell fate decision remain largely unknown. Here, we show that the expression of Ovol2, which encodes an evolutionarily conserved zinc finger transcription factor, is down-regulated during neural differentiation of mouse embryonic stem cells. Knockdown of Ovol2 in embryonic stem cells facilitates neural conversion and inhibits mesendodermal differentiation, whereas Ovol2 overexpression gives rise to the opposite phenotype. Moreover, Ovol2 knockdown partially rescues the neural inhibition and mesendodermal induction by BMP4. Mechanistic studies further show that BMP4 directly regulates Ovol2 expression through the binding of Smad1/5/8 to the second intron of the Ovol2 gene. In the chick embryo, cOvol2 expression is specifically excluded from neural territory and is up-regulated by BMP4. In addition, ectopic expression of cOvol2 in the prospective neural plate represses the expression of the definitive neural plate marker cSox2. Taken together, these results indicate that Ovol2 acts downstream of the BMP pathway in the cell fate decision between neuroectoderm and mesendoderm to ensure proper germ layer development.
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- 2013
110. The genome-wide molecular regulation of mouse gastrulation embryo
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Guangdun Peng and Naihe Jing
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0301 basic medicine ,Genetics ,Genome ,Lineage (evolution) ,Embryogenesis ,Gastrulation ,Vertebrate ,Embryonic Development ,Gene Expression Regulation, Developmental ,Context (language use) ,Embryo ,Biology ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Mice ,030104 developmental biology ,Body plan ,Evolutionary biology ,biology.animal ,Animals ,General Agricultural and Biological Sciences ,General Environmental Science ,Body Patterning - Abstract
The diverse morphologies among vertebrate species stems from the evolution of a basic body plan that is constituted by a spatially organized ensemble of tissue lineage progenitors. At gastrulation, this body plan is established through a coordinated morphogenetic process and the delineation of tissue lineages that are driven by the activity of the genome. To explore the molecular mechanisms, in a comprehensive context, it is imperative to glean an understanding of the region- and population-specific genetic activity underpinning this fundamental developmental process. In this review, we outline the recent progresses and the future directions in studies of genome activity for the regulation of mouse embryogenesis at gastrulation.
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- 2016
111. Nkx2.5 marks angioblasts that contribute to hemogenic endothelium of the endocardium and dorsal aorta
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Naihe Jing, Patrick P.L. Tam, Ralph Patrick, Thomas M. Schultheiss, Lyad Zamir, Yuliang Wang, Reena Singh, Yfat Yahalom-Ronen, Elisha Nathan, Jing-Dong J. Han, Nathan J. Palpant, Oren Yifa, Alaa A. Arraf, Richard P. Harvey, Guangdun Peng, Shengbao Suo, and Eldad Tzahor
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0301 basic medicine ,animal structures ,QH301-705.5 ,Hemangioblasts ,Science ,Chick Embryo ,Biology ,Angioblast ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Dorsal aorta ,Mice ,Spatio-Temporal Analysis ,medicine ,Animals ,Biology (General) ,Yolk sac ,hemogenic endothelium ,Aorta ,Hemogenic endothelium ,General Immunology and Microbiology ,General Neuroscience ,cardiogenesis ,General Medicine ,Anatomy ,Nkx2.5 ,Cell biology ,Endothelial stem cell ,030104 developmental biology ,medicine.anatomical_structure ,Developmental Biology and Stem Cells ,Circulatory system ,embryonic structures ,cardiovascular system ,Homeobox Protein Nkx-2.5 ,Medicine ,Hemangioblast ,Blood vessel ,Endocardium ,Research Article - Abstract
Novel regenerative therapies may stem from deeper understanding of the mechanisms governing cardiovascular lineage diversification. Using enhancer mapping and live imaging in avian embryos, and genetic lineage tracing in mice, we investigated the spatio-temporal dynamics of cardiovascular progenitor populations. We show that expression of the cardiac transcription factor Nkx2.5 marks a mesodermal population outside of the cardiac crescent in the extraembryonic and lateral plate mesoderm, with characteristics of hemogenic angioblasts. Extra-cardiac Nkx2.5 lineage progenitors migrate into the embryo and contribute to clusters of CD41+/CD45+ and RUNX1+ cells in the endocardium, the aorta-gonad-mesonephros region of the dorsal aorta and liver. We also demonstrated that ectopic expression of Nkx2.5 in chick embryos activates the hemoangiogenic gene expression program. Taken together, we identified a hemogenic angioblast cell lineage characterized by transient Nkx2.5 expression that contributes to hemogenic endothelium and endocardium, suggesting a novel role for Nkx2.5 in hemoangiogenic lineage specification and diversification. DOI: http://dx.doi.org/10.7554/eLife.20994.001, eLife digest As an animal embryo develops, it establishes a circulatory system that includes the heart, vessels and blood. Vessels and blood initially form in the yolk sac, a membrane that surrounds the embryo. These yolk sac vessels act as a rudimentary circulatory system, connecting to the heart and blood vessels within the embryo itself. In older embryos, cells in the inner layer of the largest blood vessel (known as the dorsal aorta) generate blood stem cells that give rise to the different types of blood cells. A gene called Nkx2.5 encodes a protein that controls the activity of a number of complex genetic programs and has been long studied as a key player in the development of the heart. Nkx2.5 is essential for forming normal heart muscle cells and for shaping the primitive heart and its surrounding vessels into a working organ. Interfering with the normal activity of the Nkx2.5 gene results in severe defects in blood vessels and the heart. However, many details are missing on the role played by Nkx2.5 in specifying the different cellular components of the circulatory system and heart. Zamir et al. genetically engineered chick and mouse embryos to produce fluorescent markers that could be used to trace the cells that become part of blood vessels and heart. The experiments found that some of the cells that form the blood and vessels in the yolk sac originate from within the membranes surrounding the embryo, outside of the areas previously reported to give rise to the heart. The Nkx2.5 gene is active in these cells for only a short period of time as they migrate toward the heart and dorsal aorta, where they give rise to blood stem cells These findings suggest that Nkx2.5 plays an important role in triggering developmental processes that eventually give rise to blood vessels and blood cells. The next step following on from this work will be to find out what genes the protein encoded by Nkx2.5 regulates to drive these processes. Mapping the genes that control the early origins of blood and blood-forming vessels will help biologists understand this complex and vital tissue system, and develop new treatments for patients with conditions that affect their circulatory system. In the future, this knowledge may also help to engineer synthetic blood and blood products for use in trauma and genetic diseases. DOI: http://dx.doi.org/10.7554/eLife.20994.002
- Published
- 2016
112. Dynamic Heterogeneity of Brachyury in Mouse Epiblast Stem Cells Mediates Distinct Response to Extrinsic Bone Morphogenetic Protein (BMP) Signaling*
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Ke Tang, Naihe Jing, Guangdun Peng, Jun Chen, and Lu Song
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0301 basic medicine ,Fetal Proteins ,Pluripotent Stem Cells ,Brachyury ,animal structures ,Epithelial-Mesenchymal Transition ,Cellular differentiation ,Green Fluorescent Proteins ,Germ layer ,Bone Morphogenetic Protein 4 ,Biology ,Biochemistry ,Models, Biological ,Mesoderm ,03 medical and health sciences ,Mice ,Animals ,Induced pluripotent stem cell ,Molecular Biology ,Genetics ,Endoderm ,Gene Expression Regulation, Developmental ,Cell Differentiation ,Mouse Embryonic Stem Cells ,Cell Biology ,Embryonic stem cell ,Cell biology ,030104 developmental biology ,Bone morphogenetic protein 4 ,Epiblast ,embryonic structures ,Stem cell ,Epidermis ,T-Box Domain Proteins ,Germ Layers ,Signal Transduction - Abstract
Mouse pluripotent cells, such as embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs), provide excellent in vitro systems to study imperative pre- and postimplantation events of in vivo mammalian development. It is known that mouse ESCs are dynamic heterogeneous populations. However, it remains largely unclear whether and how EpiSCs possess heterogeneity and plasticity similar to that of ESCs. Here, we show that EpiSCs are discriminated by the expression of a specific marker T (Brachyury) into two populations. The T-positive (T(+)) and the T-negative (T(-)) populations can be interconverted within the same culture condition. In addition, the two populations display distinct responses to bone morphogenetic protein (BMP) signaling and different developmental potentials. The T(-) EpiSCs are preferentially differentiated into ectoderm lineages, whereas T(+) EpiSCs have a biased potential for mesendoderm fates. Mechanistic studies reveal that T(+) EpiSCs have an earlier and faster response to BMP4 stimulation than T(-) EpiSCs. Id1 mediates the commitment of T(-) EpiSCs to epidermal lineage during BMP4 treatment. On the other hand, Snail modulates the conversion of T(+) EpiSCs to mesendoderm fates with the presence of BMP4. Furthermore, T expression is essential for epithelial-mesenchymal transition during EpiSCs differentiation. Our findings suggest that the dynamic heterogeneity of the T(+)/T(-) subpopulation primes EpiSCs toward particular cell lineages, providing important insights into the dynamic development of the early mouse embryo.
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- 2016
113. AP2γ regulates neural and epidermal development downstream of the BMP pathway at early stages of ectodermal patterning
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Yunbo Qiao, Qingqing Zhu, Ran Tao, Naihe Jing, Yue Zhu, Jun Chen, Cheng Qian, Nengyin Sheng, and Ting Zhang
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Pluripotent Stem Cells ,Embryo, Nonmammalian ,animal structures ,Neurogenesis ,Cellular differentiation ,Ectoderm ,Bone Morphogenetic Protein 4 ,Chick Embryo ,Biology ,Bone morphogenetic protein ,Nervous System ,Cell Line ,Smad1 Protein ,Mice ,medicine ,Animals ,RNA, Small Interfering ,Promoter Regions, Genetic ,Molecular Biology ,Embryonic Stem Cells ,Body Patterning ,Neurons ,Neural Plate ,integumentary system ,Gastrulation ,Gene Expression Regulation, Developmental ,Cell Differentiation ,Cell Biology ,Molecular biology ,Surface ectoderm ,Up-Regulation ,Cell biology ,medicine.anatomical_structure ,Transcription Factor AP-2 ,Bone morphogenetic protein 4 ,Epiblast ,embryonic structures ,Original Article ,RNA Interference ,Epidermis ,Neural plate ,Signal Transduction - Abstract
Bone morphogenetic protein (BMP) inhibits neural specification and induces epidermal differentiation during ectodermal patterning. However, the mechanism of this process is not well understood. Here we show that AP2γ, a transcription factor activator protein (AP)-2 family member, is upregulated by BMP4 during neural differentiation of pluripotent stem cells. Knockdown of AP2γ facilitates mouse embryonic stem cell (ESC) neural fate determination and impairs epidermal differentiation, whereas AP2γ overexpression inhibits neural conversion and promotes epidermal commitment. In the early chick embryo, AP2γ is expressed in the entire epiblast before HH stage 3 and gradually shifts to the putative epidermal ectoderm during HH stage 4. In the future neural plate AP2γ inhibits excessive neural expansion and it also promotes epidermal development in the surface ectoderm. Moreover, AP2γ knockdown in ESCs and chick embryos partially rescued the neural inhibition and epidermal induction effects of BMP4. Mechanistic studies showed that BMP4 directly regulates AP2γ expression through Smad1 binding to the AP2γ promoter. Taken together, we propose that during the early stages of ectodermal patterning in the chick embryo, AP2γ acts downstream of the BMP pathway to restrict precocious neural expansion in the prospective neural plate and initiates epidermal differentiation in the future epidermal ectoderm.
- Published
- 2012
114. Rewiring drug-activated p53-regulatory network from suppressing to promoting tumorigenesis
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Jiguang Wang, Naihe Jing, Xiang-Sun Zhang, Ying Yang, Wei Song, Luonan Chen, and Jiarui Wu
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Biology ,medicine.disease_cause ,law.invention ,Mice ,law ,Interaction network ,Cell Adhesion ,Tumor Cells, Cultured ,Genetics ,medicine ,Animals ,Gene Regulatory Networks ,Protein Interaction Maps ,Molecular Biology ,Gene ,Cell Proliferation ,Regulation of gene expression ,Cell Biology ,General Medicine ,Molecular biology ,Embryonic stem cell ,Up-Regulation ,Cell biology ,Gene Expression Regulation, Neoplastic ,Cell Transformation, Neoplastic ,P19 cell ,Apoptosis ,Gene Knockdown Techniques ,embryonic structures ,Azacitidine ,Suppressor ,Cisplatin ,Tumor Suppressor Protein p53 ,Carcinogenesis - Abstract
Many of oncogenes and tumor suppressor genes have been found to exert variable and even opposing roles in different kinds of tumors or at different stages of cancer development. Here we showed that tumorigenic potential of mouse embryonic carcinoma P19 cells cultured in adherent plates (attached-P19-cells) was suppressed by a chemotherapeutic agent, 5-aza-2'-deoxycytidine (ZdCyd), whereas the higher pro-tumorigenicity of P19 cells growing in suspension (detached-P19-cells) was generated by the ZdCyd treatment. Surprisingly, p53 activity was highly up-regulated by ZdCyd in both growing conditions. By our developed computational approaches, we revealed that there was a significant enrichment of apoptotic pathways in the ZdCyd-induced p53-dominant gene-regulatory network in attached P19 cells, whereas the pro-survival genes were significantly enriched in the ZdCyd-induced p53 network in detached P19 cells. The protein-protein interaction network of the ZdCyd-treated detached P19 cells was significantly different from that of ZdCyd-treated attached P19 cells. On the other hand, inhibition of p53 expression by siRNA suppressed the ZdCyd-induced tumorigenesis of detached P19 cells, suggesting that the ZdCyd-activated p53 plays oncogenic function in detached P19 cells. Taken together, these results indicate a context-dependent role for the ZdCyd-activated p53-dominant network in tumorigenesis.
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- 2012
115. BMP signaling pathway and spinal cord development
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Nengyin Sheng, Zhihui Xie, and Naihe Jing
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Ecology ,Neural tube patterning ,Neurogenesis ,Retinoic acid ,Wnt signaling pathway ,Anatomy ,Biology ,chemistry.chemical_compound ,medicine.anatomical_structure ,chemistry ,Genetics ,medicine ,Signal transduction ,Axon ,BMP signaling pathway ,Neuroscience ,Transcription factor ,Ecology, Evolution, Behavior and Systematics ,Biotechnology - Abstract
The development of spinal cord is a precisely and sequentially regulated process, which is controlled by signaling pathways and transcription factors in each stage. Overwhelming data have shown the essential roles of BMP signaling in different stages of this developmental process. It is also clear that the proper functions of BMP signaling require its cross-talk with several other signaling pathways including Notch, Wnt and retinoic acid (RA) pathways. Here, we highlight the recent advancement in understanding the roles of BMP signaling during neurogenesis, neural tube patterning, axon development and glial differentiation in the spinal cord, and emphasize its integrations with other pathways during these processes.
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- 2012
116. TRPC6 specifically interacts with APP to inhibit its cleavage by γ-secretase and reduce Aβ production
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Naihe Jing, Jian Yang, Yizheng Wang, Rui Lu, Zhuohao He, Junfeng Wang, Xiaomin Wang, and Hongyu Li
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Male ,General Physics and Astronomy ,Mice, Transgenic ,Cleavage (embryo) ,Article ,General Biochemistry, Genetics and Molecular Biology ,Presenilin ,Amyloid beta-Protein Precursor ,Mice ,Alzheimer Disease ,mental disorders ,Presenilin-1 ,TRPC6 Cation Channel ,Amyloid precursor protein ,Animals ,Humans ,APH-1 ,TRPC ,TRPC Cation Channels ,Amyloid beta-Peptides ,Multidisciplinary ,biology ,Chemistry ,P3 peptide ,General Chemistry ,Cell biology ,Biochemistry ,Alpha secretase ,biology.protein ,Female ,Amyloid Precursor Protein Secretases ,Amyloid precursor protein secretase ,Protein Binding - Abstract
Generation of β-amyloid (Aβ) peptide in Alzheimer's disease involves cleavage of amyloid precursor protein (APP) by γ-secretase, a protease known to cleave several substrates, including Notch. Finding specific modulators for γ-secretase could be a potential avenue to treat the disease. Here, we report that transient receptor potential canonical (TRPC) 6 specifically interacts with APP leading to inhibition of its cleavage by γ-secretase and reduction in Aβ production. TRPC6 interacts with APP (C99), but not with Notch, and prevents C99 interaction with presenilin 1 (PS1). A fusion peptide derived from TRPC6 also reduces Aβ levels without effect on Notch cleavage. Crossing APP/PS1 mice with TRPC6 transgenic mice leads to a marked reduction in both plaque load and Aβ levels, and improvement in structural and behavioural impairment. Thus, TRPC6 specifically modulates γ-secretase cleavage of APP and preventing APP (C99) interaction with PS1 via TRPC6 could be a novel strategy to reduce Aβ formation., Attempts to treat Alzheimer's disease by targeting γ-secretase cleavage of APP into Aß have been unsuccessful, partially due to off-target effects. Here, the authors identify TRPC6 as a novel γ-secretase modulator, showing that it interacts with APP to regulate Aß levels while sparing Notch cleavage.
- Published
- 2015
117. Pluripotent Stem Cell Studies Elucidate the Underlying Mechanisms of Early Embryonic Development
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Naihe Jing and Lingyu Li
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lcsh:QH426-470 ,Embryogenesis ,Wnt signaling pathway ,Nodal ,Embryo ,Review ,Germ layer ,Cell fate determination ,Biology ,Fibroblast growth factor ,Bioinformatics ,Cell biology ,Wnt ,lcsh:Genetics ,early embryonic development ,ESCs ,Genetics ,BMP ,FGF ,Induced pluripotent stem cell ,NODAL ,Genetics (clinical) ,EpiSCs - Abstract
Early embryonic development is a multi-step process that is intensively regulated by various signaling pathways. Because of the complexity of the embryo and the interactions between the germ layers, it is very difficult to fully understand how these signals regulate embryo patterning. Recently, pluripotent stem cell lines derived from different developmental stages have provided an in vitro system for investigating molecular mechanisms regulating cell fate decisions. In this review, we summarize the major functions of the BMP, FGF, Nodal and Wnt signaling pathways, which have well-established roles in vertebrate embryogenesis. Then, we highlight recent studies in pluripotent stem cells that have revealed the stage-specific roles of BMP,FGF and Nodal pathways during neural differentiation. These findings enhance our understanding of the stepwise regulation of embryo patterning by particular signaling pathways and provide new insight into the mechanisms underlying early embryonic development.
- Published
- 2011
118. FOXA2 functions as a suppressor of tumor metastasis by inhibition of epithelial-to-mesenchymal transition in human lung cancers
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Jianguo Song, Yun-Neng Tang, Naihe Jing, Guangwen Shu, and Xinwang Yuan
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Transcriptional Activation ,Epithelial-Mesenchymal Transition ,Lung Neoplasms ,Slug ,Metastasis ,Transforming Growth Factor beta1 ,Transactivation ,Cell Movement ,Cell Line, Tumor ,medicine ,Humans ,Epithelial–mesenchymal transition ,Neoplasm Metastasis ,RNA, Small Interfering ,Promoter Regions, Genetic ,Molecular Biology ,Transcription factor ,reproductive and urinary physiology ,Gene knockdown ,biology ,Cell Biology ,respiratory system ,biology.organism_classification ,medicine.disease ,Phenotype ,embryonic structures ,Hepatocyte Nuclear Factor 3-beta ,Cancer research ,Original Article ,RNA Interference ,Ectopic expression ,Snail Family Transcription Factors ,FOXA2 ,Protein Binding ,Transcription Factors - Abstract
The forkhead box transcription factor A2 (FOXA2) is an important regulator in animal development and body homeostasis. However, whether FOXA2 is involved in transforming growth factor β1 (TGF-β1)-mediated epithelial-to-mesenchymal transition (EMT) and tumor metastasis remains unknown. The present study showed that in human lung cancer cell lines, the abundance of FOXA2 positively correlates with epithelial phenotypes and negatively correlates with the mesenchymal phenotypes of cells, and TGF-β1 treatment decreased FOXA2 protein level. Consistently, knockdown of FOXA2 promoted EMT and invasion of lung cancer cells, whereas overexpression of FOXA2 reduced the invasion and suppressed TGF-β1-induced EMT. In addition, knockdown of FOXA2 induced slug expression, and ectopic expression of FOXA2 inhibited slug transcription. Furthermore, we identified that FOXA2 can bind to slug promoter through a conserved binding site, and that the DNA-binding region and transactivation region II of FOXA2 are required for repression of the slug promoter. These data demonstrate that FOXA2 functions as a suppressor of tumor metastasis by inhibition of EMT.
- Published
- 2010
119. Publisher Correction: Self-assembly of embryonic and two extra-embryonic stem cell types into gastrulating embryo-like structures
- Author
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Ran Wang, Geert Michel, Sylwia Czukiewska, Berna Sozen, Gianluca Amadei, David M. Glover, Andy Cox, Ellen Na, Naihe Jing, Magdalena Zernicka-Goetz, Thierry Voet, and Lia Chappell
- Subjects
0301 basic medicine ,Competing interests ,Statement (logic) ,Published Erratum ,Embryo ,Cell Biology ,Embryonic stem cell ,Cell biology ,03 medical and health sciences ,030104 developmental biology ,Political science ,Stem cell ,Neuroscience ,Extra embryonic - Abstract
In the version of this Technical Report originally published, the competing interests statement was missing. The authors declare no competing interests; this statement has now been added in all online versions of the Report.
- Published
- 2018
120. MicroRNA expression profiling during neural differentiation of mouse embryonic carcinoma P19 cells
- Author
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Ruqiang Liang, Naihe Jing, Caihong Xia, Botao Zhao, Bing Huang, Wei Li, Kangcheng Ruan, and Youxin Jin
- Subjects
Neurons ,Teratocarcinoma ,Gene Expression Profiling ,Biophysics ,Cell Differentiation ,Embryo ,General Medicine ,Biology ,Biochemistry ,Embryonic stem cell ,Molecular biology ,Neural stem cell ,Cell biology ,Gene Expression Regulation, Neoplastic ,Gene expression profiling ,Mice ,MicroRNAs ,P19 cell ,Downregulation and upregulation ,SOX2 ,Carcinoma, Embryonal ,Cell Line, Tumor ,microRNA ,Animals ,Oligonucleotide Array Sequence Analysis - Abstract
MicroRNAs (or miRNAs) are small non-coding RNAs (21 – 25 nucleotides) that are involved in a wide range of activities related to the development and differentiation of cells. Comparison of the miRNA expression profiles of mouse P19 embryonic carcinoma cells with those of differentiated neural stem cells showed that the expression level of 65 miRNAs changed (2-fold) after differentiation. MiR-124a was dramatically upregulated (more than 20-fold) while miRNAs of the miR-302 family and those in the miR-290 – 295 cluster were strongly down-regulated. Further analysis revealed that some important factors such as Oct4 and Sox2 appeared to be involved in the regulation of these miRNAs. These results may contribute to a better understanding of miRNA-regulated neural differentiation in early mouse embryos.
- Published
- 2009
121. Different Transcription Factors Regulate nestin Gene Expression during P19 Cell Neural Differentiation and Central Nervous System Development
- Author
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Naihe Jing, Li Liu, Wei Bian, Zhigang Jin, Leping Cheng, Guoliang Xu, and Yongfeng Chen
- Subjects
Neural Tube ,Mice, Transgenic ,Nerve Tissue Proteins ,Enhancer RNAs ,Chick Embryo ,Biology ,Response Elements ,Steroidogenic Factor 1 ,Nervous System ,Biochemistry ,Nestin ,Mice ,Intermediate Filament Proteins ,SOX2 ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Transcription, Chromatin, and Epigenetics ,Enhancer ,Molecular Biology ,Transcription factor ,Neurons ,Regulation of gene expression ,Mice, Inbred ICR ,SOXB1 Transcription Factors ,Stem Cells ,Neural tube ,Gene Expression Regulation, Developmental ,Cell Biology ,Embryo, Mammalian ,Molecular biology ,Neural stem cell ,Rats ,DNA-Binding Proteins ,medicine.anatomical_structure ,POU Domain Factors ,embryonic structures ,Chickens ,Octamer Transcription Factor-1 ,Transcription Factors - Abstract
Nestin is a molecular marker for neural progenitor cells. Rat and human nestin genes possess a central nervous system-specific enhancer within their second introns. However, the transcription factors that bind to the nestin enhancer have not been fully elucidated. Here, we show that the second intron of the mouse nestin gene is sufficient to drive reporter gene expression in the developing nervous system. The core sequence of this central nervous system-specific enhancer localizes to the 3′ 320-bp region. The cis-elements for Sox and POU family transcription factors and the hormone-responsive element are essential for nestin expression during embryonic carcinoma P19 cell neural differentiation and in the developing chick neural tube. Interestingly, different transcription factors bind to the nestin enhancer at different stages of P19 cell neural differentiation and central nervous system development. Sox2 and SF1 may mediate basal nestin expression in undifferentiated P19EC cells, whereas Sox2, Brn1, and Brn2 bind to the enhancer in P19 neural progenitor cells. Similarly, in vivo, Oct1 binds to the nestin enhancer in embryonic day 8.5 (E8.5) mouse embryos, and Oct1, Brn1, and Brn2 bind to this enhancer in E10.5 and E12.5 mouse embryos. Our studies therefore suggest a temporal coordination of transcription factors in determining nestin gene expression.
- Published
- 2009
122. Hydrogen Peroxide Promotes Aβ Production through JNK-dependent Activation of γ-Secretase
- Author
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Chengyong Shen, Ting Zhang, Huaqing Liu, Naihe Jing, Anning Lin, Kejing Zhang, and Yongfeng Chen
- Subjects
Male ,Genetically modified mouse ,Small interfering RNA ,MAP Kinase Kinase 4 ,Models, Biological ,Biochemistry ,Presenilin ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Alzheimer Disease ,Amyloid precursor protein ,medicine ,Animals ,Humans ,Senile plaques ,Enzyme Inhibitors ,Molecular Biology ,Aged ,030304 developmental biology ,Aged, 80 and over ,0303 health sciences ,biology ,Mechanisms of Signal Transduction ,P3 peptide ,Brain ,Hydrogen Peroxide ,Cell Biology ,medicine.disease ,Cell biology ,biology.protein ,Female ,Amyloid Precursor Protein Secretases ,Alzheimer's disease ,Proto-Oncogene Proteins c-akt ,Amyloid precursor protein secretase ,030217 neurology & neurosurgery - Abstract
Accumulation of senile plaques composed of amyloid beta-peptide (Abeta) is a pathological hallmark of Alzheimer disease (AD), and Abeta is generated through the sequential cleavage of amyloid precursor protein (APP) by beta- and gamma-secretase. Although oxidative stress has been implicated in the AD pathogenesis by inducing Abeta production, the underlying mechanism remains elusive. Here we show that the pro-oxidant H(2)O(2) promotes Abeta production through c-Jun N-terminal kinase (JNK)-dependent activation of gamma-secretase. Treatment with H(2)O(2) induced significant increase in the levels of intracellular and secreted Abeta in human neuroblastoma SH-SY5Y cells. Although gamma-secretase-mediated cleavage of APP or C99 was enhanced upon H(2)O(2) treatment, expression of APP or its alpha/beta-secretase-mediated cleavage was not affected. Silencing of the stress-activated JNK by small interfering RNA or the specific JNK inhibitor SP600125 reduced H(2)O(2)-induced gamma-secretase-mediated cleavage of APP. JNK activity was augmented in human brain tissues from AD patients and active JNK located surrounding the senile plaques in the brain of AD model mouse. Our data suggest that oxidative stress-activated JNK may contribute to senile plaque expansion through the promotion of gamma-secretase-mediated APP cleavage and Abeta production.
- Published
- 2008
123. rSac3, a novel Sac domain phosphoinositide phosphatase, promotes neurite outgrowth in PC12 cells
- Author
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Zhiqin Xie, Hui Zhang, Naihe Jing, Meilei Jin, Yiyuan Yuan, Bao-Ming Li, Ning Guo, Xiang Gao, and Lei Yu
- Subjects
Neurite ,Phosphatase ,Golgi Apparatus ,Cell Biology ,Biology ,Endoplasmic Reticulum ,PC12 Cells ,Gene Expression Regulation, Enzymologic ,Phosphoric Monoester Hydrolases ,Oligodeoxyribonucleotides, Antisense ,Protein Structure, Tertiary ,Rats ,Up-Regulation ,Domain (software engineering) ,Cell biology ,Protein Transport ,nervous system ,COS Cells ,Chlorocebus aethiops ,Nerve Growth Factor ,embryonic structures ,Neurites ,Animals ,Molecular Biology - Abstract
Sac domain-containing proteins belong to a newly identified family of phosphoinositide phosphatases (the PIPPase family). Despite well-characterized enzymatic activity, the biological functions of this mammalian Sac domain PIPPase family remain largely unknown. We identified a novel Sac domain-containing protein, rat Sac3 (rSac3), which is widely expressed in various tissues and localized to the endoplasmic reticulum, Golgi complex and recycling endosomes. rSac3 displays PIPPase activity with PI(3)P, PI(4)P and PI(3,5)P(2) as substrates in vitro, and a mutation in the catalytic core of the Sac domain abolishes its enzymatic activity. The expression of rSac3 is upregulated during nerve growth factor (NGF)-stimulated PC12 cell neuronal differentiation, and overexpression of this protein promotes neurite outgrowth in PC12 cells. Conversely, inhibition of rSac3 expression by antisense oligonucleotides reduces neurite outgrowth of NGF-stimulated PC12 cells, and the active site mutation of rSac3 eliminates its neurite-outgrowth-promoting activity. These results indicate that rSac3 promotes neurite outgrowth in differentiating neurons through its PIPPase activity, suggesting that Sac domain PIPPase proteins may participate in forward membrane trafficking from the endoplasmic reticulum and Golgi complex to the plasma membrane, and may function as regulators of this crucial process of neuronal cell growth and differentiation.
- Published
- 2007
124. Id Sustains Hes1 Expression to Inhibit Precocious Neurogenesis by Releasing Negative Autoregulation of Hes1
- Author
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Ge Bai, François Guillemot, Zhihui Xie, Naihe Jing, Ryoichiro Kageyama, Wei Bian, Yoshifumi Yokota, Robert Benezra, and Nengyin Sheng
- Subjects
Inhibitor of Differentiation Protein 1 ,congenital, hereditary, and neonatal diseases and abnormalities ,endocrine system ,animal structures ,Cellular differentiation ,Down-Regulation ,DEVBIO ,Proneural genes ,Chick Embryo ,Biology ,MOLNEURO ,General Biochemistry, Genetics and Molecular Biology ,Mice ,Gene expression ,Basic Helix-Loop-Helix Transcription Factors ,medicine ,Animals ,Homeostasis ,HES1 ,Promoter Regions, Genetic ,Molecular Biology ,Transcription factor ,Neurons ,Neurogenesis ,Neural tube ,Brain ,Gene Expression Regulation, Developmental ,Cell Differentiation ,Cell Biology ,STEMCELL ,Molecular biology ,Neural stem cell ,Protein Structure, Tertiary ,Up-Regulation ,Cell biology ,medicine.anatomical_structure ,embryonic structures ,Inhibitor of Differentiation Proteins ,Protein Binding ,Developmental Biology - Abstract
SummaryNegative bHLH transcription factor Hes1 can inhibit neural stem cells (NSCs) from precocious neurogenesis through repressing proneural gene expression; therefore, sustenance of Hes1 expression is crucial for NSC pool maintenance. Here we find that Ids, the dominant-negative regulators of proneural proteins, are expressed prior to proneural genes and share an overlapping expression pattern with Hes1 in the early neural tube of chick embryos. Overexpression of Id2 in the chick hindbrain upregulates Hes1 expression and inhibits proneural gene expression and neuronal differentiation. By contrast, Hes1 expression decreases, proneural gene expression expands, and neurogenesis occurs precociously in Id1;Id3 double knockout mice and in Id1–3 RNAi-electroporated chick embryos. Mechanistic studies show that Id proteins interact directly with Hes1 and release the negative feedback autoregulation of Hes1 without interfering with its ability to affect other target genes. These results indicate that Id proteins participate in NSC maintenance through sustaining Hes1 expression in early embryos.
- Published
- 2007
125. ADAM23 Plays Multiple Roles in Neuronal Differentiation of P19 Embryonal Carcinoma cells
- Author
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Naihe Jing, Kejing Deng, Yaping Sun, Jing Zhang, Chaoqun Wu, Jing Tao, Yingming Wang, Shouyi Qiao, and Chen Wang
- Subjects
Embryonal Carcinoma Stem Cells ,Cell ,Retinoic acid ,Antineoplastic Agents ,Nerve Tissue Proteins ,Tretinoin ,Neuroectodermal Cell ,Biology ,Biochemistry ,Cell Line ,Mice ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Neurofilament Proteins ,medicine ,Animals ,Neurons ,ADAM23 ,Cell Differentiation ,General Medicine ,Transfection ,Cell biology ,ADAM Proteins ,medicine.anatomical_structure ,P19 cell ,chemistry ,Cell culture ,embryonic structures ,Neoplastic Stem Cells ,RNA Interference - Abstract
ADAM23, belonging to ADAM (A Disintegrin And Metalloprotease) protein family, is mainly expressed in brain. P19 cells could differentiate into neuroectodermal cell lineage after cell aggregates have been induced by retinoic acid (RA). In this report, we show that the post-transcriptional and post-translational processes of ADAM23 are regulated during the differentiation of P19 cells. In P19-derived neurons, ADAM23 is polarized distributed in the proximal part. To explore the possible roles of ADAM23 during P19 cell neuronal differentiation, ADAM23-RNAi P19 cell lines were established. These transfected cells could differentiate into neurofilament-expression neurons in the absence of RA, whereas wild-type P19 cell can not. These results suggest ADAM23 may play roles in both early and later stage of neuronal differentiation.
- Published
- 2007
126. Epigenetic regulation of early neural fate commitment
- Author
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Naihe Jing, Yunbo Qiao, and Xianfa Yang
- Subjects
0301 basic medicine ,Central Nervous System ,Epigenetic regulation of neurogenesis ,Chromatin remodeling ,Epigenesis, Genetic ,Cell fate commitment ,Histones ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Animals ,Epigenetics ,Molecular Biology ,Pharmacology ,Genetics ,biology ,Cell Differentiation ,Cell Biology ,DNA ,Chromatin Assembly and Disassembly ,Chromatin ,030104 developmental biology ,Histone ,DNA methylation ,biology.protein ,Molecular Medicine ,RNA Interference ,Neural development ,Neuroscience ,Protein Processing, Post-Translational - Abstract
Early neural fate commitment is a key process in neural development and establishment of the central nervous system, and this process is tightly controlled by extrinsic signals, intrinsic factors, and epigenetic regulation. Here, we summarize the main findings regarding the regulatory network of epigenetic mechanisms that play important roles during early neural fate determination and embryonic development, including histone modifications, chromatin remodeling, DNA modifications, and RNA-level regulation. These regulatory mechanisms coordinate to play essential roles in silencing of pluripotency genes and activating key neurodevelopmental genes during cell fate commitment at DNA, histone, chromatin, and RNA levels. Moreover, we discuss the relationship between epigenetic regulation, signaling pathways, and intrinsic factors during early neural fate specification.
- Published
- 2015
127. AF9 promotes hESC neural differentiation through recruiting TET2 to neurodevelopmental gene loci for methylcytosine hydroxylation
- Author
-
Ran Wang, Yunbo Qiao, Fang Yu, Y. Eugene Chin, Xianfa Yang, Naihe Jing, Lu Song, Guoliang Xu, Yuanyuan Li, and Xiongjun Wang
- Subjects
Genetics ,5-Hydroxymethylcytosine ,Regulation of gene expression ,TET2 ,neural differentiation ,Mechanism (biology) ,human embryonic stem cell ,Cell Biology ,Biology ,Biochemistry ,Embryonic stem cell ,Article ,AF9 ,Cell biology ,chemistry.chemical_compound ,chemistry ,Histone methylation ,5-hydroxymethylcytosine ,Molecular Biology ,Neural development ,Gene ,reproductive and urinary physiology ,Function (biology) - Abstract
AF9 mutations have been implicated in human neurodevelopmental diseases and murine Af9 mediates histone methylation during cortical neuron generation. However, AF9 function and related mechanisms in human neurodevelopment remain unknown. Here we show that AF9 is necessary and sufficient for human embryonic stem cell (hESC) neural differentiation and neurodevelopmental gene activation. The 5-methylcytosine (5mC) dioxygenase TET2, which was identified in an AF9-associated protein complex, physically interacted with AF9. Both AF9 and TET2 co-localized in 5-hydroxymethylcytosine (5hmC)-positive hESC-derived neurons and were required for appropriate hESC neural differentiation. Upon binding to AAC-containing motifs, AF9 recruited TET2 to occupy the common neurodevelopmental gene loci to direct 5mC-to-5hmC conversion, which was followed by sequential activation of neural target genes and hESC neural commitment. These findings define an AF9–TET2 regulatory complex for modulating human neural development and reveal a novel mechanism by which the AF9 recognition specificity and TET2 hydroxylation activity cooperate to control neurodevelopmental gene activation.
- Published
- 2015
128. Genome-wide ChIP-seq and RNA-seq analyses of Pou3f1 during mouse pluripotent stem cell neural fate commitment
- Author
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Jing-Dong J. Han, Na Sun, Guangdun Peng, Naihe Jing, Jun Chen, and Lu Song
- Subjects
Mouse embryonic stem cell ,lcsh:QH426-470 ,Wnt signaling pathway ,Neural Inhibition ,RNA-Seq ,Computational biology ,Biology ,Bioinformatics ,Biochemistry ,Genome ,ChIP-seq ,lcsh:Genetics ,SOX2 ,Data in Brief ,Genetics ,Molecular Medicine ,RNA-seq ,Induced pluripotent stem cell ,Pou3f1 ,Gene ,Transcription factor ,Biotechnology ,Neural fate commitment - Abstract
Appropriate neural initiation of the pluripotent stem cells in the early embryos is critical for the development of the central nervous system. This process is regulated by the coordination of extrinsic signals and intrinsic programs. However, how the coordination is achieved to ensure proper neural fate commitment is largely unknown. Here, taking advantage of genome-wide ChIP-sequencing (ChIP-seq) and RNA-sequencing (RNA-seq) analyses, we demonstrate that the transcriptional factor Pou3f1 is an upstream activator of neural-promoting genes, and it is able to repress neural-inhibitory signals as well. Further studies revealed that Pou3f1 could directly bind neural lineage genes like Sox2 and downstream targets of neural inhibition signaling such as BMP and Wnt. Our results thus identify Pou3f1 as a critical dual-regulator of the intrinsic transcription factors and the extrinsic cellular signals during neural fate commitment. Data were deposited in Gene Expression Omnibus (GEO) datasets under reference number GSE69865.
- Published
- 2015
129. Histone deacetylation promotes mouse neural induction by restricting Nodal-dependent mesendoderm fate
- Author
-
Lingbo Wang, Lu Song, Naihe Jing, Jun Chen, Fang Yu, Ke Tang, Jing-Dong J. Han, Yunbo Qiao, Guangdun Peng, Chang Liu, Can Xing, Pingyu Liu, Yuxuan Wu, Jinsong Li, Chunmei Yue, and Xiaoyang Dou
- Subjects
Chromatin Immunoprecipitation ,Nodal Protein ,Neurogenesis ,Blotting, Western ,General Physics and Astronomy ,Histone Deacetylase 1 ,In Vitro Techniques ,Biology ,Cell fate determination ,General Biochemistry, Genetics and Molecular Biology ,Epigenesis, Genetic ,Histones ,Mesoderm ,Mice ,Animals ,RNA, Messenger ,Epigenetics ,Embryonic Stem Cells ,Oligonucleotide Array Sequence Analysis ,Multidisciplinary ,Histone deacetylase 2 ,Endoderm ,Gene Expression Regulation, Developmental ,General Chemistry ,Molecular biology ,HDAC1 ,Cell biology ,Gastrulation ,Histone ,Acetylation ,embryonic structures ,biology.protein ,CRISPR-Cas Systems ,Chromatin immunoprecipitation ,Germ Layers - Abstract
Cell fate determination requires the cooperation between extrinsic signals and intrinsic molecules including transcription factors as well as epigenetic regulators. Nevertheless, how neural fate commitment is regulated by epigenetic modifications remains largely unclear. Here we show that transient histone deacetylation at epiblast stage promotes neural differentiation of mouse embryonic stem cells (mESCs). Histone deacetylase 1 (HDAC1) deficiency in mESCs partially phenocopies the inhibition of histone deacetylation in vitro, and displays reduced incorporation into neural tissues in chimeric mouse embryos in vivo. Mechanistic studies show that Nodal, which is repressed by histone deacetylation, is a direct target of HDAC1. Furthermore, the inhibition of histone deacetylation in the anterior explant of mouse embryos at E7.0 leads to Nodal activation and neural development repression. Thus, our study reveals an intrinsic mechanism that epigenetic histone deacetylation ensures neural fate commitment by restricting Nodal signalling in murine anterior epiblast ex vivo and mESC in vitro.
- Published
- 2015
130. Mediator Med23 deficiency enhances neural differentiation of murine embryonic stem cells through modulating BMP signaling
- Author
-
Naihe Jing, Lu Song, Yan Liang, Dan Liang, Jinsong Li, Gang Wang, Wanqu Zhu, and Xiao Yao
- Subjects
Chromatin Immunoprecipitation ,Cell ,Blotting, Western ,Cell- and Tissue-Based Therapy ,Fluorescent Antibody Technique ,Biology ,Real-Time Polymerase Chain Reaction ,MED1 ,Mice ,Mediator ,medicine ,Animals ,Molecular Biology ,Embryonic Stem Cells ,In Situ Hybridization ,Neurons ,Gene knockdown ,Mediator Complex ,Gene Expression Profiling ,Cell Differentiation ,Neurodegenerative Diseases ,Microarray Analysis ,Embryonic stem cell ,Cell biology ,medicine.anatomical_structure ,Cell Fate Control ,Gene Knockdown Techniques ,embryonic structures ,Bone Morphogenetic Proteins ,Endoderm ,Neural development ,Developmental Biology ,Signal Transduction - Abstract
Unraveling the mechanisms underlying early neural differentiation of embryonic stem cells (ESCs) is crucial to developing cell-based therapies of neurodegenerative diseases. Neural fate acquisition is proposed to be controlled by a ‘default’ mechanism, for which the molecular regulation is not well understood. In this study, we investigated the functional roles of Mediator Med23 in pluripotency and lineage commitment of murine ESCs. Unexpectedly, we found that, despite the largely unchanged pluripotency and self-renewal of ESCs, Med23 depletion rendered the cells prone to neural differentiation in different differentiation assays. Knockdown of two other Mediator subunits, Med1 and Med15, did not alter the neural differentiation of ESCs. Med15 knockdown selectively inhibited endoderm differentiation, suggesting the specificity of cell fate control by distinctive Mediator subunits. Gene profiling revealed that Med23 depletion attenuated BMP signaling in ESCs. Mechanistically, MED23 modulated Bmp4 expression by controlling the activity of ETS1, which is involved in Bmp4 promoter-enhancer communication. Interestingly, med23 knockdown in zebrafish embryos also enhanced neural development at early embryogenesis, which could be reversed by co-injection of bmp4 mRNA. Taken together, our study reveals an intrinsic, restrictive role of MED23 in early neural development, thus providing new molecular insights for neural fate determination.
- Published
- 2015
131. Cell Aggregation-induced FGF8 Elevation Is Essential for P19 Cell Neural Differentiation
- Author
-
Wei Lin, Siew-Lan Ang, Ye-Guang Chen, Caihong Xia, Naihe Jing, Wei Bian, Chen Wang, and Li Liu
- Subjects
Pluripotent Stem Cells ,animal structures ,Fibroblast Growth Factor 8 ,Smad6 Protein ,Cellular differentiation ,Biology ,Fibroblast growth factor ,Bone morphogenetic protein ,Mice ,Carcinoma, Embryonal ,Cell Line, Tumor ,Animals ,Pyrroles ,RNA, Small Interfering ,Protein Kinase Inhibitors ,Molecular Biology ,Cell Aggregation ,Neurons ,Cell Differentiation ,Articles ,Cell Biology ,Embryonic stem cell ,Cell aggregation ,Up-Regulation ,BMPR2 ,P19 cell ,Bone Morphogenetic Proteins ,embryonic structures ,Cancer research ,RNA Interference ,Stem cell ,Signal Transduction - Abstract
FGF8, a member of the fibroblast growth factor (FGF) family, has been shown to play important roles in different developing systems. Mouse embryonic carcinoma P19 cells could be induced by retinoic acid (RA) to differentiate into neuroectodermal cell lineages, and this process is cell aggregation dependent. In this report, we show that FGF8 expression is transiently up-regulated upon P19 cell aggregation, and the aggregation-dependent FGF8 elevation is pluripotent stem cell related. Overexpressing FGF8 promotes RA-induced monolayer P19 cell neural differentiation. Inhibition of FGF8 expression by RNA interference or blocking FGF signaling by the FGF receptor inhibitor, SU5402, attenuates neural differentiation of the P19 cell. Blocking the bone morphogenetic protein (BMP) pathway by overexpressing Smad6 in P19 cells, we also show that FGF signaling plays a BMP inhibition–independent role in P19 cell neural differentiation.
- Published
- 2006
132. Second Intron of Mouse Nestin Gene Directs its Expression in Pluripotent Embryonic Carcinoma Cells through POU Factor Binding Site
- Author
-
Li Liu, Leping Cheng, Naihe Jing, Wei Bian, Kejing Zhang, Yongfeng Chen, Hua Zhong, and Zhigang Jin
- Subjects
Pluripotent Stem Cells ,Cellular differentiation ,Biophysics ,Nerve Tissue Proteins ,Biology ,Biochemistry ,Nestin ,Mice ,Intermediate Filament Proteins ,Tumor Cells, Cultured ,Animals ,Enhancer ,Gene ,Reporter gene ,Binding Sites ,Base Sequence ,POU domain ,Carcinoma ,Gene Expression Regulation, Developmental ,DNA ,General Medicine ,Molecular biology ,Embryonic stem cell ,Introns ,Neural stem cell ,Enhancer Elements, Genetic ,Mutation ,POU Domain Factors ,embryonic structures - Abstract
Nestin, an intermediate filament protein, is expressed in the neural stem cells of the developing central nervous system. This tissue-specific expression is driven by the neural stem cell-specific enhancer in the second intron of the nestin gene. In this study, we showed that the mouse nestin gene was expressed in pluripotent embryonic carcinoma (EC) P19 and F9 cells, not in the differentiated cell types. This cell type-specific expression was conferred by the enhancer in the second intron. Mutation of the conserved POU factor-binding site in the enhancer abolished the reporter gene expression in EC cells. Oct4, a Class V POU factor, was found to be coexpressed with nestin in EC cells. Electrophoretic mobility-shift assays and supershift assays showed that a unique protein-DNA complex was formed specifically with nuclear extracts of EC cells, and Oct4 protein was included. Together, these results suggest the functional relevance between the conserved POU factor-binding site and the expression of the nestin gene in pluripotent EC cells.
- Published
- 2006
133. The negative cell cycle regulator, Tob (transducer of ErbB-2), is involved in motor skill learning
- Author
-
Xue-Han Zhang, Xiang Gao, Lei Yu, Bao-Ming Li, Naihe Jing, Xin-Ming Wang, Meilei Jin, Guoping Zhao, and Yan-Yang Tu
- Subjects
Male ,Cerebellum ,Central nervous system ,Biophysics ,Hippocampus ,Cell Cycle Proteins ,Biology ,Biochemistry ,Feedback ,Rats, Sprague-Dawley ,ErbB ,Task Performance and Analysis ,medicine ,Animals ,Learning ,Tissue Distribution ,Molecular Biology ,Motor skill ,Cell cycle regulator ,Cell Biology ,Cell cycle ,Rats ,Repressor Proteins ,medicine.anatomical_structure ,Motor Skills ,Rotarod Performance Test ,Memory consolidation ,Neuroscience - Abstract
Tob (transducer of ErbB-2) is a negative cell cycle regulator with anti-proliferative activity in peripheral tissues. Our previous study identified Tob as a protein involved in hippocampus-dependent memory consolidation (M.L. Jin, X.M. Wang, Y.Y. Tu, X.H. Zhang, X. Gao, N. Guo, Z.Q. Xie, G.P. Zhao, N.H. Jing, B.M. Li, Y.Yu, The negative cell cycle regulator, Tob (Transducer of ErbB-2), is a multifunctional protein involved in hippocampus-dependent learning and memory, Neuroscience 131 (2005) 647-659). Here, we provide evidence that Tob in the central nervous system is engaged in acquisition of motor skill. Tob has a relatively high expression in the cerebellum. Tob expression is up-regulated in the cerebellum after rats receive training on a rotarod-running task. Rats infused with Tob antisense oligonucleotides into the 4th ventricle exhibit a severe deficit in running on a rotating rod or walking across a horizontally elevated beam.
- Published
- 2006
134. Inhibition of Transforming Growth Factor β (TGF-β) Signaling can Substitute for Oct4 Protein in Reprogramming and Maintain Pluripotency*
- Author
-
Saber Mohamed Abd-Allah, Naihe Jing, Cheng Qian, Fangzhi Tan, and Ke Tang
- Subjects
MAPK/ERK pathway ,animal structures ,Cellular differentiation ,Blotting, Western ,Induced Pluripotent Stem Cells ,MAP Kinase Kinase 1 ,Fluorescent Antibody Technique ,Dioxoles ,Fibroblast growth factor ,Real-Time Polymerase Chain Reaction ,Biochemistry ,Mice ,Transforming Growth Factor beta ,Animals ,RNA, Messenger ,Induced pluripotent stem cell ,Extracellular Signal-Regulated MAP Kinases ,Molecular Biology ,Cells, Cultured ,Embryonic Stem Cells ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,Wnt signaling pathway ,Cell Differentiation ,Transforming growth factor beta ,Cell Biology ,Fibroblasts ,Cellular Reprogramming ,Embryo, Mammalian ,Embryonic stem cell ,Cell biology ,Mice, Inbred C57BL ,embryonic structures ,Benzamides ,biology.protein ,Fibroblast Growth Factor 1 ,Reprogramming ,Octamer Transcription Factor-3 ,Signal Transduction - Abstract
Mouse pluripotent stem cells (PSCs), such as ES cells and induced PSCs (iPSCs), are an excellent system to investigate the molecular and cellular mechanisms involved in early embryonic development. The signaling pathways orchestrated by leukemia inhibitor factor/STAT3, Wnt/β-catenin, and FGF/MEK/ERK play key roles in the generation of pluripotency. However, the function of TGF-β signaling in this process remains elusive. Here we show that inhibiting TGF-β signaling with its inhibitor SB431542 can substitute for Oct4 during reprogramming. Moreover, inhibiting TGF-β signaling can sustain the pluripotency of iPSCs and ES cells through modulating FGF/MEK/ERK signaling. Therefore, this study reveals a novel function of TGF-β signaling inhibition in the generation and maintenance of PSCs.
- Published
- 2014
135. Ectodermal progenitors derived from epiblast stem cells by inhibition of Nodal signaling
- Author
-
Ran Wang, Guangdun Peng, Ke Tang, Naihe Jing, Janet Rossant, Lingyu Li, Pingyu Liu, Jun Chen, Chang Liu, and Lu Song
- Subjects
animal structures ,Nodal Protein ,Cellular differentiation ,Nodal signaling ,Ectoderm ,Germ layer ,Bone Morphogenetic Protein 4 ,Biology ,Mice ,Pregnancy ,Genetics ,medicine ,Animals ,Molecular Biology ,Embryonic Stem Cells ,Neuroectoderm ,Gene Expression Regulation, Developmental ,Cell Differentiation ,Cell Biology ,General Medicine ,Embryo, Mammalian ,Cell biology ,Gastrulation ,medicine.anatomical_structure ,Epiblast ,embryonic structures ,Female ,Stem cell ,Germ Layers ,Signal Transduction - Abstract
The ectoderm has the capability to generate epidermis and neuroectoderm and plays imperative roles during the early embryonic development. Our recent study uncovered a region with ectodermal progenitor potential in mouse embryo at embryonic day 7.0 and revealed that Nodal inhibition is essential for its formation. Here, we demonstrate that through brief inhibition of Nodal signaling in vitro, mouse embryonic stem cell (ESC)-derived epiblast stem cells (ESD-EpiSCs) could be committed to transient ectodermal progenitor populations, which possess the ability to give rise to neural or epidermal ectoderm in the absence or presence of BMP4, respectively. Mechanistic studies reveal that BMP4 recruits distinct transcriptional targets in ESD-EpiSCs and ectoderm-like cells. Furthermore, FGF-Erk signaling may also be alleviated during the generation of ectoderm-like cells. Thus, our data suggest that instructive interactions among several extracellular signals participate in the commitment of ectoderm from ESD-EpiSCs, which shed new light on the understanding of the formation of ectoderm during the gastrulation in early mouse embryo development.
- Published
- 2014
136. Intrinsic regulations in neural fate commitment
- Author
-
Guangdun Peng, Naihe Jing, Yunbo Qiao, Ke Tang, and Lu Song
- Subjects
Genetics ,Pluripotent Stem Cells ,Epigenetic regulation of neurogenesis ,Ectoderm ,Cell Biology ,Biology ,Fibroblast growth factor ,Nervous System ,Cell biology ,Mesoderm ,Mice ,medicine.anatomical_structure ,SOX2 ,embryonic structures ,Histone methylation ,DNA methylation ,medicine ,Animals ,Humans ,Epigenetics ,Neural plate ,Embryonic Stem Cells ,Developmental Biology ,Transcription Factors - Abstract
Neural fate commitment is an early embryonic event that a group of cells in ectoderm, which do not ingress through primitive streak, acquire a neural fate but not epidermal or mesodermal lineages. Several extracellular signaling pathways initiated by the secreted proteins bone morphogenetic proteins (BMPs), fibroblast growth factors (FGFs), wingless/int class proteins (WNTs) and Nodal play essential roles in the specification of the neural plate. Accumulating evidence from the studies on mouse and pluripotent embryonic stem cells reveals that except for the extracellular signals, the intracellular molecules, including both transcriptional and epigenetic factors, participate in the modulation of neural fate commitment as well. In the review, we mainly focus on recent findings that the initiation of the nervous system is elaborately regulated by the intrinsic programs, which are mediated by transcriptional factors such as Sox2, Zfp521, Sip1 and Pou3f1, as well as epigenetic modifications, including histone methylation/demethylation, histone acetylation/deacetylation, and DNA methylation/demethylation. The discovery of the intrinsic regulatory machineries provides better understanding of the mechanisms by which the neural fate commitment is ensured by the cooperation between extracellular factors and intracellular molecules.
- Published
- 2014
137. Fhos2, a novel formin-related actin-organizing protein, probably associates with the nestin intermediate filament
- Author
-
Naihe Jing, Ryu Takeya, Norinobu Watanabe, Kosei Takeuchi, Hideki Kanaya, and Hideki Sumimoto
- Subjects
Vimentin ,macromolecular substances ,Cell Biology ,Biology ,Nestin ,Microfilament ,Molecular biology ,Cell biology ,Formins ,Genetics ,biology.protein ,MDia1 ,Cytoskeleton ,Intermediate filament ,Actin - Abstract
Fhos1 is a mammalian formin-family protein, and functions as an organizer of the actin microfilament. Here we have cloned human and mouse cDNAs for a novel Fhos homolog, designated Fhos2. The messages for Fhos2 are expressed in the heart, kidney, and brain, where the Fhos1 mRNAs are not abundant. Two splice variants of Fhos2 exist in a tissue-specific manner; the longer variant Fhos2L is the major form in the heart, whereas the kidney and brain predominantly express Fhos2S that encodes a shorter protein. Over-expression of an active form of the two Fhos2 variants, as well as that of Fhos1, induces the formation of actin stress fibers in HeLa cells, suggesting that Fhos2 acts as an actin-organizing protein. Biochemical analysis using rat cardiomyoblastic H9c2 (2-1) cells reveals that endogenous Fhos2 is enriched in the intermediate filament fraction. Consistent with this, Fhos2 localizes to the nestin intermediate filament but not to other cytoskeletons, as demonstrated by staining of H9c2 (2-1) cells with anti-Fhos2 antibodies. Furthermore, Fhos2 is present in nestin-expressing neuroepithelial cells of the fetal rat brain. Thus, Fhos2 not only has the actin-organizing activity but also associates with nestin, which may imply a Fhos2-mediated link between the nestin intermediate filament and actin microfilament.
- Published
- 2005
138. Moderate hypothermia prevents neural cell apoptosis following spinal cord ischemia in rabbits
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Zhi Yun Xu, Liang Jian Zou, Lei Ming Wang, Ye Yan, and Naihe Jing
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Programmed cell death ,Necrosis ,Ischemia ,Apoptosis ,DNA Fragmentation ,Biology ,Neuroprotection ,Hypothermia, Induced ,In Situ Nick-End Labeling ,medicine ,Animals ,Humans ,Molecular Biology ,Neurons ,Spinal Cord Ischemia ,Cell Biology ,Hypothermia ,medicine.disease ,Spinal cord ,medicine.anatomical_structure ,Proto-Oncogene Proteins c-bcl-2 ,Anesthesia ,Rabbits ,Tumor Suppressor Protein p53 ,medicine.symptom ,Paraplegia - Abstract
Paraplegia is a disastrous complication after operations of descending and thoracoabdominal aortic aneurysm. Regional hypothermia protects against spinal cord ischemia although the protective mechanism is not well know. The objective of this study is to examine whether hypothermia protects the spinal cord by preventing apoptosis of nerve cell and also investigate a possible mechanism involved in hypothermia neuroprotection. Cell apoptosis with necrosis was evident in the spinal cord 24 h after 30 min of ischemia. Moderate hypothermia decreased the incidence of apoptotic nerve cells. Both cell apoptosis and necrosis were attenuated by hypothermia. p53 expression increased and bcl-2 expression declined after ischemia, while hypothermia mitigated these changes. This study suggests that apoptosis contributes to cell death after spinal cord ischemia, and that moderate hypothermia can prevent nerve cell apoptosis by a mechanism associated with bcl-2 and p53 genes.
- Published
- 2005
139. The negative cell cycle regulator, Tob (transducer of ErbB-2), is a multifunctional protein involved in hippocampus-dependent learning and memory
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Meilei Jin, Bao-Ming Li, Naihe Jing, Xiaoxiao Gao, Yan-Yang Tu, Zhiqin Xie, Xin-Ming Wang, N. Guo, Lei Yu, Guoping Zhao, and Xue-Han Zhang
- Subjects
Male ,Time Factors ,Blotting, Western ,Conditioning, Classical ,Long-Term Potentiation ,Central nervous system ,Oligonucleotides ,Gene Expression ,Morris water navigation task ,Hippocampus ,Rats, Sprague-Dawley ,Mice ,ErbB ,Avoidance Learning ,Reaction Time ,medicine ,Animals ,Humans ,Amino Acid Sequence ,Cloning, Molecular ,Maze Learning ,Gene Library ,Mice, Inbred BALB C ,Mice, Inbred ICR ,Cell cycle regulator ,Base Sequence ,Behavior, Animal ,General Neuroscience ,Memoria ,Intracellular Signaling Peptides and Proteins ,Excitatory Postsynaptic Potentials ,Long-term potentiation ,Fear ,Oligonucleotides, Antisense ,Cell cycle ,Blotting, Northern ,Rats ,medicine.anatomical_structure ,Animals, Newborn ,Gene Expression Regulation ,Antisense oligonucleotides ,Carrier Proteins ,Psychology ,Neuroscience - Abstract
Tob (transducer of ErbB2) is a negative cell cycle regulator with anti-proliferative activity in the periphery. Using a behavioral screening paradigm to look for novel gene functions in the brain, we identified Tob as a brain-expressed protein involved in learning and memory. Behavioral training of fear-conditioning triggered a transient elevation of Tob protein, which preceded the formation of long-term memory. Functional perturbation of Tob by intra-CA1 infusion of antisense oligonucleotides in rats impaired spatial learning and memory in the Morris water maze and long-term memory for contextual fear conditioning, two behavioral paradigms that require the hippocampus. Furthermore, long-term potentiation was suppressed by Tob antisense infusion into the CA1 region. Together, these results indicate that the negative cell cycle regulator Tob is a multifunctional protein involved in hippocampus-dependent learning and memory.
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- 2005
140. Identification and Characterization of a Rat Novel Gene RSEP4 Expressed Specifically in Central Nervous System
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Lingwei Kong, Lei Yu, Naihe Jing, Zhi-Qi Zhao, Zhi-Xin Lin, Zhiqin Xie, Yu-Qiu Zhang, and Xidao Wang
- Subjects
Messenger RNA ,HEK 293 cells ,Central nervous system ,Biophysics ,General Medicine ,In situ hybridization ,Biology ,Biochemistry ,Molecular biology ,Fusion protein ,Open reading frame ,medicine.anatomical_structure ,Complementary DNA ,medicine ,Northern blot - Abstract
The low-abundantly expressed genes composed the majorities of the mRNAs expressed in the central nervous system (CNS), and were thought to be important for the normal brain functions. Through differential screening a low-abundance cDNA sublibrary with mRNA from neuropathic pain of chronic constriction injury (CCI) model, we have identified a novel rat gene, rat spinal-cord expression protein 4 gene (RSEP4). The total length of RSEP4 cDNA is 2006 bp, with a 501 nucleotide open reading frame (ORF) that encodes a 167 amino acid polypeptide. Northern blot revealed that RSEP4 was expressed specifically in the CNS. In situ hybridization showed that the mRNA of RSEP4 was strongly expressed in the CA1, CA2, CA3 and DG regions of hippocampus, the Purkinje cells of cerebellum, and the small sensory neurons of dorsal horn and large motor neurons of ventral horn of spinal cord. Over-expression of RSEP4-EGFP fusion protein in the human embryonic kidney 293T cells showed that RSEP4 protein was mainly localized in the cell cytoplasm. These results suggest that RSEP4 may play some roles in the CNS.
- Published
- 2004
141. Characterization and promoter analysis of the mouse nestin gene
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Ye Yan, Leping Cheng, Naihe Jing, Tingting Li, Li Liu, Xueliang Zhu, and Zhigang Jin
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Transcription, Genetic ,P19 cell ,Biochemistry ,Nestin ,Mice ,Intermediate Filament Proteins ,Genes, Reporter ,Structural Biology ,Transcription (biology) ,Cricetinae ,Luciferases ,Promoter Regions, Genetic ,Neurons ,Mouse nestin gene ,Stem Cells ,Brain ,Neural stem cell ,DNA-Binding Proteins ,Sp3 Transcription Factor ,Plasmids ,DNA, Complementary ,Sp1 Transcription Factor ,Molecular Sequence Data ,Biophysics ,Sp3 ,Nerve Tissue Proteins ,CHO Cells ,Biology ,Sp1 ,Cell Line ,Sp3 transcription factor ,Cell Line, Tumor ,Genetics ,Animals ,Humans ,Electrophoretic mobility shift assay ,Luciferase ,Molecular Biology ,Gene ,DNA Primers ,Binding Sites ,Base Sequence ,Promoter ,Cell Biology ,Molecular biology ,Mutagenesis, Site-Directed ,NIH 3T3 Cells ,RNA ,Poly A ,Transcription Factors - Abstract
The intermediate filament protein nestin is expressed in the neural stem cells of the developing central nervous system (CNS). Promoter analysis revealed that the minimal promoter of the mouse nestin gene resides in the region −11 to +183 of the 5′-non-coding and upstream flanking region, and that two adjacent Sp1-binding sites are necessary for promoter activity. Electrophoretic mobility-shift assays (EMSA) and supershift assays showed that Sp1 and Sp3 proteins selectively bind to the upstream Sp1 site. These results demonstrate an important functionality of Sp1 and Sp3 in regulating the expression of the mouse nestin gene.
- Published
- 2004
142. Cloning of the mouse Sef gene and comparative analysis of its expression with Fgf8 and Spry2 during embryogenesis
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Maximillian Fürthauer, Bernard Thisse, Siew-Lan Ang, Wei Lin, Christine Thisse, and Naihe Jing
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Embryology ,animal structures ,DNA, Complementary ,Time Factors ,Fibroblast Growth Factor 8 ,Molecular Sequence Data ,Branchial arch ,Biology ,Protein Serine-Threonine Kinases ,Limb bud ,Mice ,FGF8 ,Animals ,Amino Acid Sequence ,Cloning, Molecular ,Gene ,In Situ Hybridization ,Adaptor Proteins, Signal Transducing ,Cloning ,Sequence Homology, Amino Acid ,Synexpression ,Intracellular Signaling Peptides and Proteins ,Brain ,Membrane Proteins ,Proteins ,Embryo ,Blotting, Northern ,Molecular biology ,Fibroblast Growth Factors ,Protein Biosynthesis ,embryonic structures ,Forebrain ,Developmental Biology - Abstract
We report the cloning and expression analysis of a mouse gene encoding a novel transmembrane protein. Expression of Sef is similar to that of Fgf8 and Spry2 during early embryogenesis, being prominent in the forebrain, mid-hindbrain boundary, branchial arches, somites, limb bud and tailbud of mouse embryos. These expression profiles indicate that Fgf8, Spry2 and Sef belong to a synexpression group and suggest that these genes may functionally interact during embryonic development. From E12.5 onwards, partially distinct patterns of expression of these genes are observed in the neuroepithelium, sense organs and endodermal-derived organs, that are known sites of expression of other Fgfs.
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- 2002
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143. The transcription factor Pou3f1 promotes neural fate commitment via activation of neural lineage genes and inhibition of external signaling pathways
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Naihe Jing, Ke Tang, Guangdun Peng, Yunbo Qiao, Na Sun, Jing-Dong J. Han, Jun Chen, Jinsong Li, Ting Zhang, Wei Tang, Cheng Qian, Lu Song, Nengyin Sheng, and Qingqing Zhu
- Subjects
Chromatin Immunoprecipitation ,QH301-705.5 ,Science ,Cellular differentiation ,chicken ,Green Fluorescent Proteins ,Embryoid body ,Chick Embryo ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Mice ,Neural Stem Cells ,neural fate commitment ,Neurosphere ,Animals ,pluripotent stem cell ,Cell Lineage ,Biology (General) ,BMP/Wnt pathway ,mouse ,Embryonic Stem Cells ,Neural Plate ,General Immunology and Microbiology ,Sequence Analysis, RNA ,General Neuroscience ,Cell Differentiation ,General Medicine ,extrinsic signal ,Molecular biology ,Neural stem cell ,Cell biology ,Endothelial stem cell ,Neuroepithelial cell ,Wnt Proteins ,Developmental Biology and Stem Cells ,BMP/Wnt pathways ,embryonic structures ,Bone Morphogenetic Proteins ,Medicine ,Octamer Transcription Factor-6 ,intrinsic factor ,Stem cell ,Pou3f1 ,Germ Layers ,Adult stem cell ,Research Article ,Signal Transduction - Abstract
The neural fate commitment of pluripotent stem cells requires the repression of extrinsic inhibitory signals and the activation of intrinsic positive transcription factors. However, how these two events are integrated to ensure appropriate neural conversion remains unclear. In this study, we showed that Pou3f1 is essential for the neural differentiation of mouse embryonic stem cells (ESCs), specifically during the transition from epiblast stem cells (EpiSCs) to neural progenitor cells (NPCs). Chimeric analysis showed that Pou3f1 knockdown leads to a markedly decreased incorporation of ESCs in the neuroectoderm. By contrast, Pou3f1-overexpressing ESC derivatives preferentially contribute to the neuroectoderm. Genome-wide ChIP-seq and RNA-seq analyses indicated that Pou3f1 is an upstream activator of neural lineage genes, and also is a repressor of BMP and Wnt signaling. Our results established that Pou3f1 promotes the neural fate commitment of pluripotent stem cells through a dual role, activating internal neural induction programs and antagonizing extrinsic neural inhibitory signals. DOI: http://dx.doi.org/10.7554/eLife.02224.001, eLife digest After an egg has been fertilized, it undergoes a series of divisions to produce a ball of cells known as a blastocyst. The cells within the blastocyst are pluripotent stem cells, which have the potential to become many different types of cell. After a few days, the stem cells organize into three layers—an innermost layer called the endoderm, a middle layer of mesoderm, and an outer layer of ectoderm—that ultimately give rise to different types of tissues. The brain and nervous system are formed from cells in the neuroectoderm, which is part of the ectoderm. Now, Zhu et al. have shown that a transcription factor called Pou3f1 triggers stem cells within a region of the ectoderm to turn into neural progenitor cells, thereby generating the neuroectoderm. These neural progenitor cells then go on to become neurons and glial cells that make up the brain and nervous system. Using a virus to reduce levels of Pou3f1 in embryonic stem cells grown in a dish led to a drop in the number of stem cells that committed to neural progenitor cells. Overexpressing Pou3f1 in the stem cells restored the number of neural progenitor cells. Together these results showed that Pou3f1 is both necessary and sufficient for the conversion of embryonic stem cells into future neurons and glia. The same result was seen when embryonic stem cells containing either reduced or elevated levels of Pou3f1 were injected into 2.5-day-old mouse blastocysts, which were then implanted into surrogate females. The resulting embryos comprised some cells with normal levels of Pou3f1, and others with either too little or too much. Cells with elevated Pou3f1 mostly became neural progenitors, whereas those with reduced levels rarely did so. Gene expression studies revealed that Pou3f1 promoted the formation of neural progenitor cells by activating the expression of pro-neuronal genes inside the stem cells, and by blocking anti-neuronal pathways called Wnt/BMP signaling cascades initiated outside the cells. By revealing the two roles of Pou3f1, Zhu et al. have increased our understanding of one of the earliest stages of nervous system development. Further work is required to determine exactly how Pou3f1 exerts its effects and, in particular, whether it performs its two roles simultaneously or in sequence. DOI: http://dx.doi.org/10.7554/eLife.02224.002
- Published
- 2014
144. Author response: The transcription factor Pou3f1 promotes neural fate commitment via activation of neural lineage genes and inhibition of external signaling pathways
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Qingqing Zhu, Lu Song, Guangdun Peng, Na Sun, Jun Chen, Ting Zhang, Nengyin Sheng, Wei Tang, Cheng Qian, Yunbo Qiao, Ke Tang, Jing-Dong Jackie Han, Jinsong Li, and Naihe Jing
- Published
- 2014
145. Mouse nestin cDNA cloning and protein expression in the cytoskeleton of transfected cells
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Leping Cheng, Naihe Jing, Wei Bian, Jing Yang, Yasuhiro Tomooka, Ye Yan, and Robert Shiurba
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DNA, Complementary ,Recombinant Fusion Proteins ,Green Fluorescent Proteins ,Molecular Sequence Data ,Biophysics ,Nerve Tissue Proteins ,macromolecular substances ,Biology ,Transfection ,Biochemistry ,Nestin ,Mice ,Intermediate Filament Proteins ,Structural Biology ,Complementary DNA ,Genetics ,Animals ,Amino Acid Sequence ,Northern blot ,Cloning, Molecular ,Peptide sequence ,Cytoskeleton ,Southern blot ,Messenger RNA ,Molecular biology ,Fusion protein ,Neural stem cell ,Luminescent Proteins ,Gene Expression Regulation ,COS Cells ,Sequence Alignment - Abstract
Complementary DNA (cDNA) corresponding to mouse nestin intermediate filament protein, a specific marker for neural stem cells, was isolated and characterized. The complete sequence comprised 5983 base pairs encoding 1821 amino acids, and the deduced polypeptide was similar to rat (84%), hamster (73%), and human (62%) nestin. Southern blots showed that mouse nestin was a single-copy gene, and Northern blots detected a 6.0 kilobase mRNA transcript. When the cDNA was overexpressed as an enhanced green fluorescent fusion protein in COS7 cells, nestin immunoreactivity appeared in the filamentous cytoskeletal network. Accordingly, biologically active mouse nestin cDNA may offer an important new tool for stem cell research.
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- 2001
146. Maternal zinc deficiency impairs brain nestin expression in prenatal and postnatal mice
- Author
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Jun Sheng Guo, Fa Ji Zhao, Naihe Jing, Wei Bian, Fudi Wang, and Lingwei Kong
- Subjects
Aging ,medicine.medical_specialty ,Offspring ,chemistry.chemical_element ,Nerve Tissue Proteins ,Zinc ,Biology ,Nestin ,Mice ,Fetus ,Intermediate Filament Proteins ,Pregnancy ,Internal medicine ,medicine ,Animals ,Molecular Biology ,Food, Formulated ,Mice, Inbred ICR ,Stem Cells ,Neural tube ,Brain ,Gene Expression Regulation, Developmental ,Cell Differentiation ,Cell Biology ,medicine.disease ,Immunohistochemistry ,Neural stem cell ,medicine.anatomical_structure ,Endocrinology ,Animals, Newborn ,chemistry ,Cerebral cortex ,Zinc deficiency ,Female - Abstract
Effects of maternal dietary zinc deficiency on prenatal and postnatal brain development were investigated in ICR strain mice. From d 1 of pregnancy (E0) until postnatal d 20 (P20), maternal mice were fed experimental diets that contained 1 mg Zn/kg/day (severe zinc deficient, SZD), 5 mg Zn/kg/day (marginal zinc deficient, MZD), 30 mg Zn/kg/day (zinc adequately supplied, ZA) or 100 mg Zn/kg/day (zinc supplemented, ZS and pair-fed, PF). Brains of offspring from these dietary groups were examined at various developmental stages for expression of nestin, an intermediate filament protein found in neural stem cells and young neurons. Immunocytochemistry showed nestin expression in neural tube 10.5 d post citrus (dpc) as well as in the cerebral cortex and neural tube from 10.5 dpc to postnatal d 10 (P10). Nestin immunoreactivities in both brain and neural tube of those zinc-supplemented control groups (ZA, ZS, PF) were stronger than those in zinc-deficient groups (SZD and MZD). Western blot analysis confirmed that nestin levels in pooled brain extracts from each of the zinc-supplemented groups (ZA, ZS, PF) were much higher than those from the zinc-deficient groups (SZD and MZD) from 10.5 dpc to P10. Immunostaining and Western blots showed no detectable nestin in any of the experimental and control group brains after P20. These observations of an association between maternal zinc deficiency and decreased nestin protein levels in brains of offspring suggest that zinc deficiency suppresses development of neural stem cells, an effect which may lead to neuroanatomical and behavioral abnormalities in adults.
- Published
- 2001
147. Mouse nestin protein localizes in growth cones of P19 neurons and cerebellar granule cells
- Author
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Ye Yan, Naihe Jing, Wei Bian, and Jing Yang
- Subjects
Cerebellum ,Neurite ,Growth Cones ,Intermediate Filaments ,Fluorescent Antibody Technique ,Nerve Tissue Proteins ,macromolecular substances ,Biology ,Filamentous actin ,Nestin ,Mice ,GAP-43 Protein ,Intermediate Filament Proteins ,Carcinoma, Embryonal ,Tumor Cells, Cultured ,medicine ,Animals ,Axon ,Gap-43 protein ,Growth cone ,Mice, Inbred ICR ,General Neuroscience ,Age Factors ,Cell Differentiation ,Cell biology ,Neuroepithelial cell ,medicine.anatomical_structure ,nervous system ,embryonic structures ,biology.protein ,Microtubule-Associated Proteins ,Neuroscience - Abstract
The neuronal growth cone, a highly motile structure at the distal tip of growing axons, contains filamentous actin and microtubules as its main cytoskeletal components. Using immunocytochemistry, we observed that nestin, which is the predominant intermediate filament protein in neuroepithelial cells and young neurons of the developing brain, appears to be strongly expressed in neurites and growth cones of neurons differentiating from P19 embryonic carcinoma cells in vitro. Double-staining of nestin and microtubule-associated protein-2 as well as nestin and growth-associated protein-43 revealed that nestin protein localizes in neurites and the central regions of growth cones of primary cultures of cerebellar granule cells from postnatal day 6 mice. These results suggest a role for nestin in growth cone guidance during axon elongation.
- Published
- 2001
148. Nestin expression during mouse eye and lens development
- Author
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Leping Chen, Naihe Jing, Jing Yang, Wei Bian, and Xiang Gao
- Subjects
Embryology ,genetic structures ,Molecular Sequence Data ,Nerve Tissue Proteins ,In situ hybridization ,Biology ,Eye ,Nestin ,Mice ,Intermediate Filament Proteins ,Lens, Crystalline ,medicine ,Animals ,Optic stalk ,RNA, Messenger ,reproductive and urinary physiology ,Gene Expression Regulation, Developmental ,Anatomy ,eye diseases ,Lens Fiber ,Cell biology ,medicine.anatomical_structure ,Lens (anatomy) ,embryonic structures ,Optic nerve ,Eye development ,sense organs ,Optic disc ,Developmental Biology - Abstract
Nestin is an intermediate filament protein, which is expressed predominantly in the developing central nervous system and skeletal muscles. In situ hybridization revealed that mouse nestin mRNA is in the optic stalk at 9.0 days post coitus (dpc) and in the lens vesicle at 10.0 dpc. From 14.5 dpc onward, nestin transcripts appear in lens fibers and neuroretina. Immunohistochemistry showed that nestin protein appears in the optic stalk at 9.5 dpc and in the posterior lens epithelium at 10.5 dpc. By 12.5 dpc, it is found in the lens, neuroretina, and optic stalk as well as in developing extrinsic ocular muscle, and it localizes in lens epithelium, optic disc, and optic nerve from 14.5 dpc to postnatal day 1. In adult eye, nestin protein appears in the optic nerve.
- Published
- 2000
- Full Text
- View/download PDF
149. Genome-wide analysis of histone acetylation dynamics during mouse embryonic stem cell neural differentiation
- Author
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Xiaoyang Dou, Naihe Jing, Pingyu Liu, Jing-Dong J. Han, and Guangdun Peng
- Subjects
Mouse embryonic stem cell ,Histone deacetylase 5 ,Epigenetic regulation of neurogenesis ,lcsh:QH426-470 ,Histone deacetylase 2 ,SAP30 ,Biology ,Biochemistry ,HDAC4 ,Molecular biology ,Histone deacetylase 1 ,ChIP-sequence ,Cell biology ,lcsh:Genetics ,Histone methyltransferase ,Data in Brief ,Histone H2A ,Genetics ,Molecular Medicine ,Histone H3 acetylation ,Neural fate commitment ,Biotechnology - Abstract
Epigenetic modification as an intrinsic fine-tune program cooperates with key transcription factors to regulate the cell fate determination. The histone acetylation participating in neural differentiation of pluripotent stem cells is expected but not well studied. Here, using acetylated histone H3 ChIP-sequencing (ChIP-seq), we demonstrate that the histone H3 acetylation level is gradually increased on the neural gene loci while decreased on the neural-inhibitory gene loci during mouse embryonic stem cell (mESC) neural differentiation. We further show that histone deacetylase 1 (HDAC1) is essential for neural commitment by targeting Nodal signaling. Thus, our study reveals a mechanism by which the epigenetic modification of histone acetylation/deacetylation interacts with extracellular signaling in mESC neural fate determination. Data were deposited in Gene Expression Omnibus (GEO) datasets under reference number GSE66025.
- Published
- 2015
150. TGFβ signaling hyperactivation-induced tumorigenicity during the derivation of neural progenitors from mouse ESCs.
- Author
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Xianfa Yang, Ran Wang, Xiongjun Wang, Guoqing Cai, Yun Qian, Su Feng, Fangzhi Tan, Kun Chen, Ke Tang, Xingxu Huang, Naihe Jing, and Yunbo Qiao
- Abstract
Clinical therapies of pluripotent stem cells (PSCs)-based transplantation have been hindered by frequent development of teratomas or tumors in animal models and clinical patients. Therefore, clarifying the mechanism of carcinogenesis in stem cell therapy is of great importance for reducing the risk of tumorigenicity. Here we differentiate Oct4-GFP mouse embryonic stem cells (mESCs) into neural progenitor cells (NPCs) and find that a minority of Oct4+ cells are continuously sustained at Oct4+ state. These cells can be enriched and proliferated in a standard ESC medium. Interestingly, the differentiation potential of these enriched cells is tightly restricted with much higher tumorigenic activity, which are thus defined as differentiation-resistant ESCs (DR-ESCs). Transcriptomic and epigenomic analyses show that DR-ESCs are characterized by primordial germ cell-like gene signatures (Dazl, Rec8, Stra8, Blimp1, etc.) and specific epigenetic patterns distinct from mESCs. Moreover, the DR-ESCs possess germ cell potential to generate Sycp3+ haploid cells and are able to reside in sperm-free spermaduct induced by busulfan. Finally, we find that TGFβ signaling is overactivated in DR-ESCs, and inhibition of TGFβ signaling eliminates the tumorigenicity of mESC-derived NPCs by inducing the full differentiation of DR-ESCs. These data demonstrate that these TGFβ-hyperactivated germ cell-like DR-ESCs are the main contributor for the tumorigenicity of ESCs-derived target cell therapy and that inhibition of TGFβ signaling in ESC-derived NPC transplantation could drastically reduce the risk of tumor development. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
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