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Abstract Studies of laminopathy-based progeria offer insights into aging-associated diseases and highlight the role of LMNA in chromatin organization. Mandibuloacral dysplasia type A (MAD) is a largely unexplored form of atypical progeria that lacks lamin A post-translational processing defects. Using iPSCs derived from a male MAD patient carrying homozygous LMNA p.R527C, premature aging phenotypes are recapitulated in multiple mesenchymal lineages, including mesenchymal stem cells (MSCs). Comparison with 26 human aging MSC expression datasets reveals that MAD-MSCs exhibit the highest similarity to senescent primary human MSCs. Lamina-chromatin interaction analysis reveals reorganization of lamina-associating domains (LADs) and repositioning of non-LAD binding peaks may contribute to the observed accelerated senescence. Additionally, 3D genome organization further supports hierarchical chromatin disorganization in MAD stem cells, alongside dysregulation of genes involved in epigenetic modification, stem cell fate maintenance, senescence, and geroprotection. Together, these findings suggest LMNA missense mutation is linked to chromatin alterations in an atypical progeroid syndrome.

Abstract The genome is intricately folded into chromatin compartments, topologically associating domains (TADs) and loops unique to each cell type. How this higher-order genome organization regulates cell fate transition remains elusive. Here we show how a single non-neural progenitor transcription factor, PTF1A, reorchestrates the 3D genome during fibroblast transdifferentiation into neural stem cells (NSCs). Multiomics analyses integrating Hi-C data, PTF1A and CTCF DNA-binding profiles, H3K27ac modification, and gene expression, demonstrate that PTF1A binds to subTAD boundaries subsequently associated with elevated CTCF binding and enhanced boundary insulation, and reorganizes chromatin loops, leading to gene expression changes that drive transdifferentiation into NSCs. Moreover, PTF1A activates enhancers and super-enhancers near low-insulation boundaries and modulates H3K27ac deposition, promoting cell fate transitions. Together, our data implicate an involvement of 3D genome in transcriptional and cell fate alterations, and highlight an essential role for PTF1A in gene expression control and multiscale 3D genome remodeling during cell reprogramming.

Abstract CCCTC-binding factor (CTCF), a ubiquitously expressed and highly conserved protein, is known to play a critical role in chromatin structure. Post-translational modifications (PTMs) diversify the functions of protein to regulate numerous cellular processes. However, the effects of PTMs on the genome-wide binding of CTCF and the organization of three-dimensional (3D) chromatin structure have not been fully understood. In this study, we uncovered the PTM profiling of CTCF and demonstrated that CTCF can be O-GlcNAcylated and arginine methylated. Functionally, we demonstrated that O-GlcNAcylation inhibits CTCF binding to chromatin. Meanwhile, deficiency of CTCF O-GlcNAcylation results in the disruption of loop domains and the alteration of chromatin loops associated with cellular development. Furthermore, the deficiency of CTCF O-GlcNAcylation increases the expression of developmental genes and negatively regulates maintenance and establishment of stem cell pluripotency. In conclusion, these results provide key insights into the role of PTMs for the 3D chromatin structure.

Abstract Understanding intracellular phase separation is crucial for deciphering transcriptional control, cell fate transitions, and disease mechanisms. However, the key residues, which impact phase separation the most for protein phase separation function have remained elusive. We develop PSPHunter, which can precisely predict these key residues based on machine learning scheme. In vivo and in vitro validations demonstrate that truncating just 6 key residues in GATA3 disrupts phase separation, enhancing tumor cell migration and inhibiting growth. Glycine and its motifs are enriched in spacer and key residues, as revealed by our comprehensive analysis. PSPHunter identifies nearly 80% of disease-associated phase-separating proteins, with frequent mutated pathological residues like glycine and proline often residing in these key residues. PSPHunter thus emerges as a crucial tool to uncover key residues, facilitating insights into phase separation mechanisms governing transcriptional control, cell fate transitions, and disease development.

Liver organoids are three-dimensional cellular tissue models in which cells interact to form unique structures in culture. During the past 10 years, liver organoids with various cellular compositions, structural features, and functional properties have been described. Methods to create these advanced human cell models range from simple tissue culture techniques to complex bioengineering approaches. Liver organoid culture platforms have been used in various research fields, from modeling liver diseases to regenerative therapy. This review discusses how liver organoids are used to model disease, including hereditary liver diseases, primary liver cancer, viral hepatitis, and nonalcoholic fatty liver disease. Specifically, we focus on studies that used either of two widely adopted approaches: differentiation from pluripotent stem cells or epithelial organoids cultured from patient tissues. These approaches have enabled the generation of advanced human liver models and, more importantly, the establishment of patient-tailored models for evaluating disease phenotypes and therapeutic responses at the individual level.

Abstract Cell fate transition is a fascinating process involving complex dynamics of three-dimensional (3D) chromatin organization and phase separation, which play an essential role in cell fate decision by regulating gene expression. Phase separation is increasingly being considered a driving force of chromatin folding. In this review, we have summarized the dynamic features of 3D chromatin and phase separation during physiological and pathological cell fate transitions and systematically analyzed recent evidence of phase separation facilitating the chromatin structure. In addition, we discuss current advances in understanding how phase separation contributes to physical and functional enhancer-promoter contacts. We highlight the functional roles of 3D chromatin organization and phase separation in cell fate transitions, and more explorations are required to study the regulatory relationship between 3D chromatin organization and phase separation. Graphical Abstract 3D chromatin organization (shown by Hi-C contact map) and phase separation are highly dynamic and play functional roles during early embryonic development, cell differentiation, somatic reprogramming, cell transdifferentiation and pathogenetic process. Phase separation can regulate 3D chromatin organization directly, but whether 3D chromatin organization regulates phase separation remains unclear.

In this study, we present a straightforward and highly effective photo-triggered hydrogenation method for aryl halides, devoid of transition-metal catalysts. Through the synergistic utilization of light, PhNHNH2, and a base, we have successfully initiated the desired radical-mediated hydrogenation process. Remarkably, utilizing mild reaction conditions, a wide range of aryl halides, including fluorides, chlorides, bromides, and iodides, can be selectively transformed into their corresponding (hetero)arene counterparts, with exceptional yields. Additionally, this approach demonstrates a remarkable compatibility with diverse functional groups and heterocyclic compounds, highlighting its versatility and potential for use in various chemical transformations.

Genome topology provides a structural basis for epigenome-mediated transcriptional regulation in eukaryotes. Here the authors characterized the 3D genome of stratified squamous epithelia. They generated a Hi-C map of human limbal stem/progenitor cells (LSCs) and integrated these data with epigenomics, transcription factor binding maps, and transcriptome data.

Abstract Background Biomolecular condensates have been implicated in multiple cellular processes. However, the global role played by condensates in 3D chromatin organization remains unclear. At present, 1,6-hexanediol (1,6-HD) is the only available tool to globally disrupt condensates, yet the conditions of 1,6-HD vary considerably between studies and may even trigger apoptosis. Results In this study, we first analyzed the effects of different concentrations and treatment durations of 1,6-HD and found that short-term exposure to 1.5% 1,6-HD dissolved biomolecular condensates whereas long-term exposure caused aberrant aggregation without affecting cell viability. Based on this condition, we drew a time-resolved map of 3D chromatin organization and found that short-term treatment with 1.5% 1,6-HD resulted in reduced long-range interactions, strengthened compartmentalization, homogenized A-A interactions, B-to-A compartment switch and TAD reorganization, whereas longer exposure had the opposite effects. Furthermore, the long-range interactions between condensate-component-enriched regions were markedly weakened following 1,6-HD treatment. Conclusions In conclusion, our study finds a proper 1,6-HD condition and provides a resource for exploring the role of biomolecular condensates in 3D chromatin organization.

Although the interactors of pluripotency factors have been identified in mouse embryonic stem cells (ESCs), their interactors in human ESCs remain unexplored. Here the authors map OCT4 protein interactions in naïve and primed human ESCs to find specific interactions with BAF subunits that promote an open chromatin architecture at blastocyst-associated genes and ectodermal genes, respectively.

Abstract Climate warming is known to impact ecosystem composition and functioning. However, it remains largely unclear how soil microbial communities respond to long-term, moderate warming. In this study, we used Illumina sequencing and microarrays (GeoChip 5.0) to analyze taxonomic and functional gene compositions of the soil microbial community after 14 years of warming (at 0.8–1.0 °C for 10 years and then 1.5–2.0 °C for 4 years) in a Californian grassland. Long-term warming had no detectable effect on the taxonomic composition of soil bacterial community, nor on any plant or abiotic soil variables. In contrast, functional gene compositions differed between warming and control for bacterial, archaeal, and fungal communities. Functional genes associated with labile carbon (C) degradation increased in relative abundance in the warming treatment, whereas those associated with recalcitrant C degradation decreased. A number of functional genes associated with nitrogen (N) cycling (e.g., denitrifying genes encoding nitrate-, nitrite-, and nitrous oxidereductases) decreased, whereas nifH gene encoding nitrogenase increased in the warming treatment. These results suggest that microbial functional potentials are more sensitive to long-term moderate warming than the taxonomic composition of microbial community.

Corneal epithelium shares similar molecular signatures to other stratified epithelia. Here, the authors map super-enhancers and accessible chromatin in corneal epithelium, identifying a transcription regulatory circuit, including RUNX1, PAX6, and SMAD3, required for corneal epithelial identity and homeostasis.

The aim of this study is to analyze the variations in the plant-available nitrogen (PAN) concentrations in the soil profile. Different fertilizers were applied for Chinese cabbage plantation (CCP) in the experimental fields of the Shunyi region. The treatments used for the comparative analysis are (i) no fertilizer and plantation (NVP), (ii) no fertilizer with CCP (CTP), (iii) fertilization as urea (URP), and (iv) potassium nitrate (KNP) and chicken manure (CMP) with CCP. It was concluded that the yield was significantly high in URP, CMP, and KNP as compared to CTP. In URP, maximum PAN in soil layers 0–60 cm was recorded during crop production and in 60–100 cm after harvesting as compared to other treatments. Significant variations in soil pH and electrical conductivity (EC) for the soil profile (0–100 cm) from the initial values with respect to time and treatments were observed. CMP showed maximum ammonium in the upper layers of 0–60 cm throughout the season, whereas minimum PAN was observed in NVP but increased in lower layers of 60–100 cm. In general, all fertilizers raised the PAN below the soil 60–100 cm which indicates their potential for nitrate leaching (NL).

Summary: Phase separation of proteins regulates transcription. Here, we present a protocol to manipulate phase separation capacity of a protein. We use this protocol to disrupt phase separation by mutating residues at intrinsically disordered regions (IDRs). Further, we rescue the disabled phase separation by fusing an IDR known to drive phase separation. Phase separation promotes cell fate transitions, whereas disruption of phase attenuates the transitions. The major challenge is how to effectively predict mutation residues.For complete details on the use and execution of this protocol, please refer to Wang et al. (2021).

Summary: Reorganization of topologically associated domain (TAD) is considered to be a novel mechanism for cell fate transitions. Here, we present a protocol to manipulate TAD via abscisic acid (ABA)-dependent genome linking. We use this protocol to merge two adjacent TADs and evaluate the influence on cell fate transitions. The advantages are that the manipulation does not change the genome and is reversible by withdrawing ABA. The major challenge is how to select linking loci for efficient TAD reorganization.For complete details on the use and execution of this protocol, please refer to Wang et al. (2021).

ABSTRACT Polycomb group (PcG) ring finger protein 6 (PCGF6), though known as a member of the transcription-repressing complexes, PcG, also has activation function in regulating pluripotency gene expression. However, the mechanism underlying the activation function of PCGF6 is poorly understood. Here, we found that PCGF6 co-localizes to gene activation regions along with pluripotency factors such as OCT4. In addition, PCGF6 was recruited to a subset of the super-enhancer (SE) regions upstream of cell cycle-associated genes by OCT4, and increased their expression. By combining with promoter capture Hi-C data, we found that PCGF6 activates cell cycle genes by regulating SE-promoter interactions via 3D chromatin. Our findings highlight a novel mechanism of PcG protein in regulating pluripotency, and provide a research basis for the therapeutic application of pluripotent stem cells.

Understanding species responsiveness to anthropogenic environmental changes benefits the guide to manage biodiversity. Microbes are traditionally thought to be more sensitive to environmental changes than plants. However, this hypothesis is supported by little empirical evidence. We compared plant and microbial responses to 13 types of simulated environmental changes (mowing (M), adding nitrogen (N), adding phosphorus (P), watering (W), warming (T) and combinations of these) in a steppe ecosystem. Contrary to our hypothesis, the microbial responses were generally smaller than the plant responses to different types of environmental changes, both at the community-abundance level and species/operational taxonomic unit (OTU)/gene level. This might be ascribed to the soil buffering capacity to environmental changes, and the rapid evolutionary adaptation for microbial communities. Furthermore, the responses at the community-abundance level were larger than at the species/OTU/gene level to 13 types of environmental changes, both in plant and microbial communities. Given that the community abundance representing the total number of all individuals of the organism within the community, the responses to environmental changes at the community-abundance level is likely to be larger than at the species/OTU/gene level. Plant biomass was more responsive to N addition, particularly in such N- limiting grassland ecosystem. Our findings highlight that plant communities are more responsive to environmental changes than microbial communities, contrary to the traditional viewpoint. Therefore, plant communities could be used as ecological indicators of anthropogenic environmental changes in grasslands. Keywords: Plant community, Microbial community, Anthropogenic environmental changes, Grassland, Abundance, Species/OTU/Gene number

ABSTRACT Sialylation, or the covalent addition of sialic acid to the terminal end of glycoproteins, is a biologically important modification that is involved in embryonic development, neurodevelopment, reprogramming, oncogenesis and immune responses. In this review, we have given a comprehensive overview of the current literature on the involvement of sialylation in cell fate decision during development, reprogramming and cancer progression. Sialylation is essential for early embryonic development and the deletion of UDP-GlcNAc 2-epimerase, a rate-limiting enzyme in sialic acid biosynthesis, is embryonically lethal. Furthermore, the sialyltransferase ST6GAL1 is required for somatic cell reprogramming, and its downregulation is associated with decreased reprogramming efficiency. In addition, sialylation levels and patterns are altered during cancer progression, indicating the potential of sialylated molecules as cancer biomarkers. Taken together, the current evidences demonstrate that sialylation is involved in crucial cell fate decision.

Uhrf1 is a known regulator of heterochromatin and DNA methylation in embryonic stem cells (ESCs). Here, the authors demonstrate that Uhrf1 acts together with the Set1/COMPASS complex regulator of active transcription to promote H3K4 methylation at bivalent loci and Uhrf1 loss results in disruption of differentiation.

Liver organogenesis requires complex cell-cell interactions between hepatic endoderm cells and adjacent cell niches. Endothelial cells are key players for endoderm hepatic fate decision. We previously demonstrated that the endothelial cell niche promotes hepatic specification of mouse embryonic stem cell(ESC)-derived endoderm through dual repression of Wnt and Notch pathways in endoderm cells. In the present study, we dissected further the mechanisms by which endothelial cells trigger endoderm hepatic specification. Using our previously established in vitro mouse ESC system mimicking the early hepatic specification process, endoderm cells were purified and co-cultured with endothelial cells to induce hepatic specification. The comparison of transcriptome profiles between hepatic endoderm cells isolated from co-cultures and endoderm cells cultured alone revealed that VEGF signaling instructs hepatic specification of endoderm cells through endothelial VEGFR2 activation. Additionally, epigenetic mark inhibition assays upon co-cultures uncovered that histone acetylation and DNA methylation promote hepatic specification while histone methylation inhibits it. This study provides an efficient 2D platform modelling the endothelial cell niche crosstalk with endoderm, and reveals mechanisms by which endothelial cells promote hepatic specification of mouse ESC-derived endoderm cells through endothelial VEGFR2 activation and endoderm epigenetic modifications. Keywords: Mouse embryonic stem cells, Endoderm hepatic specification, Endothelial cells, VEGFR2, Epigenetic modifications

Summary: Yin Yang 1 (YY1) regulates early embryogenesis and adult tissue formation. However, the role of YY1 in stem cell regulation remains unclear. YY1 has a Polycomb group (PcG) protein-dependent role in mammalian cells. The PcG-independent functions of YY1 are also reported, although their underlying mechanism is still undefined. This paper reports the role of YY1 and BAF complex in the OCT4-mediated pluripotency network in mouse embryonic stem cells (mESCs). The interaction between YY1 and BAF complex promotes mESC proliferation and pluripotency. Knockdown of Yy1 or Smarca4, the core component of the BAF complex, downregulates pluripotency markers and upregulates several differentiation markers. Moreover, YY1 enriches at both promoter and super-enhancer regions to stimulate transcription. Thus, this study elucidates the role of YY1 in regulating pluripotency through its interaction with OCT4 and the BAF complex and the role of BAF complex in integrating YY1 into the core pluripotency network. : In this article, Junjun Ding and colleagues show the role of YY1 in regulating embryonic stem cells through its interaction with OCT4 and the BAF complex to activate transcription, promote ESC proliferation, and maintain pluripotency, and the role of BAF complex in integrating YY1 into the core pluripotency network. Keywords: YY1, polycomb, the BAF complex, super-enhancer, pluripotency, Oct4, interactome, cell cycle

Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) is a long and inefficient process. A thorough understanding of the molecular mechanisms underlying reprogramming is paramount for efficient generation and safe application of iPSCs in medicine. While intensive efforts have been devoted to identifying reprogramming facilitators and barriers, a full repertoire of such factors, as well as their mechanistic actions, is poorly defined. Here, we report that NAC1, a pluripotency-associated factor and NANOG partner, is required for establishment of pluripotency during reprogramming. Mechanistically, NAC1 is essential for proper expression of E-cadherin by a dual regulatory mechanism: it facilitates NANOG binding to the E-cadherin promoter and fine-tunes its expression; most importantly, it downregulates the E-cadherin repressor ZEB1 directly via transcriptional repression and indirectly via post-transcriptional activation of the miR-200 miRNAs. Our study thus uncovers a previously unappreciated role for the pluripotency regulator NAC1 in promoting efficient somatic cell reprogramming.

The core pluripotency transcription factor NANOG is critical for embryonic stem cell (ESC) self-renewal and somatic cell reprogramming. Although NANOG is phosphorylated at multiple residues, the role of NANOG phosphorylation in ESC self-renewal is incompletely understood, and no information exists regarding its functions during reprogramming. Here we report our findings that NANOG phosphorylation is beneficial, although nonessential, for ESC self-renewal, and that loss of phosphorylation enhances NANOG activity in reprogramming. Mutation of serine 65 in NANOG to alanine (S65A) alone has the most significant impact on increasing NANOG reprogramming capacity. Mechanistically, we find that pluripotency regulators (ESRRB, OCT4, SALL4, DAX1, and TET1) are transcriptionally primed and preferentially associated with NANOG S65A at the protein level due to presumed structural alterations in the N-terminal domain of NANOG. These results demonstrate that a single phosphorylation site serves as a critical interface for controlling context-dependent NANOG functions in pluripotency and reprogramming.

Although SIN3A is required for the survival of early embryos and embryonic stem cells (ESCs), the role of SIN3A in the maintenance and establishment of pluripotency remains unclear. Here, we find that the SIN3A/HDAC corepressor complex maintains ESC pluripotency and promotes the generation of induced pluripotent stem cells (iPSCs). Members of the SIN3A/HDAC corepressor complex are enriched in an extended NANOG interactome and function in transcriptional coactivation in ESCs. We also identified a critical role for SIN3A and HDAC2 in efficient reprogramming of somatic cells. Mechanistically, NANOG and SIN3A co-occupy transcriptionally active pluripotency genes in ESCs and also co-localize extensively at their genome-wide targets in pre-iPSCs. Additionally, both factors are required to directly induce a synergistic transcriptional program wherein pluripotency genes are activated and reprogramming barrier genes are repressed. Our findings indicate a transcriptional regulatory role for a major HDAC-containing complex in promoting pluripotency.

The response of microbial communities to continual and prolonged water exposure provides useful insight when facing global climate changes that cause increased and uneven precipitation and extreme rainfall events. In this study, we investigated an in situ manipulative experiment with four levels of water exposure (ambient precipitation +0%, +25%, +50%, and +100% of local annual mean precipitation) in a desert ecosystem of China. After 9 years of water addition, Illumina sequencing was used to analyze taxonomic compositions of the soil bacterial, archaeal, and fungal communities. The results showed significant increases in microbial biomass carbon (MBC) at higher amended precipitation levels, with the highest values reported at 100% precipitation. Furthermore, an increase in the bacterial species richness was observed along the water addition gradient. In addition, the relative abundance of several bacterial phyla, such as Proteobacteria, significantly increased, whereas that of some drought-tolerant taxa, including Actinobacteria, Firmicutes, and Bacteroidetes, decreased. In addition, the phyla Planctomycetes and Nitrospirae, associated with nitrification, positively responded to increased precipitation. Archaeal diversity significantly reduced under 100% treatment, with changes in the relative abundance of Thaumarchaeota and Euryarchaeota being the main contributors to shifts in the archaeal community. The fungal community composition was stable in response to water addition. Results from the Mantel test and structural equation models suggested that bacterial and archaeal communities reacted contrastingly to water addition. Bacterial community composition was directly affected by changing soil moisture and temperature, while archaeal community composition was indirectly affected by changing nitrogen availability. These findings highlight the importance of soil moisture and nitrogen in driving microbial responses to long-term precipitation changes in the desert ecosystem.

We report on a novel fabrication approach of metal nanowires with complex surface. Taking advantage of nodular growth triggered by the presence of surface defects created intentionally on the substrate as well as the high tilt angle between the magnetron source axis and the normal to the substrate, metal nanowires containing hillocks emerging out of the surface can be created. The approach is demonstrated for several metals and alloys including gold, copper, silver, gold–copper and gold–silver. We demonstrate that applying an electrochemical dealloying process to the gold–copper alloy nanowire arrays allows for transforming the hillocks into ring-like shaped nanopores. The resulting porous gold nanowires exhibit a very high roughness and high specific surface making of them a promising candidate for the development of SERS-based sensors.

Ten-eleven translocation (Tet) family proteins convert 5-methylcytosine to 5-hydroxymethylcytosine. We show that mouse embryonic stem cells (ESCs) depleted of Tet1 and/or Tet2 by RNAi exhibit short telomeres and chromosomal instability, concomitant with reduced telomere recombination. Tet1 and Tet2 double-knockout ESCs also display short telomeres but to a lesser extent. Notably, Tet1/2/3 triple-knockout ESCs show heterogeneous telomere lengths and increased frequency of telomere loss and chromosomal fusion. Mechanistically, Tets depletion or deficiency increases Dnmt3b and decreases 5hmC levels, resulting in elevated methylation levels at sub-telomeres. Consistently, knockdown of Dnmt3b or addition of 2i (MAPK and GSK3β inhibitors), which also inhibits Dnmt3b, reduces telomere shortening, partially rescuing Tet1/2 deficiency. Interestingly, Tet1/2 double or Tet1/2/3 triple knockout in ESCs consistently upregulates Zscan4, which may counteract telomere shortening. Together, Tet enzymes play important roles in telomere maintenance and chromosomal stability of ESCs by modulating sub-telomeric methylation levels.

In this paper, we review the current development of stencil lithography for scalable micro- and nanomanufacturing as a resistless and reusable patterning technique. We first introduce the motivation and advantages of stencil lithography for large-area micro- and nanopatterning. Then we review the progress of using rigid membranes such as SiNx and Si as stencil masks as well as stacking layers. We also review the current use of flexible membranes including a compliant SiNx membrane with springs, polyimide film, polydimethylsiloxane (PDMS) layer, and photoresist-based membranes as stencil lithography masks to address problems such as blurring and non-planar surface patterning. Moreover, we discuss the dynamic stencil lithography technique, which significantly improves the patterning throughput and speed by moving the stencil over the target substrate during deposition. Lastly, we discuss the future advancement of stencil lithography for a resistless, reusable, scalable, and programmable nanolithography method.

Somatic cell nuclear transfer (SCNT) has been proved capable of reprogramming various differentiated somatic cells into pluripotent stem cells. Recently, induced pluripotent stem cells (iPS) have been successfully derived from mouse and human somatic cells by the over-expression of a combination of transcription factors. However, the molecular mechanisms underlying the reprogramming mediated by either the SCNT or iPS approach are poorly understood. Increasing evidence indicates that many tumor pathways play roles in the derivation of iPS cells. Embryonal carcinoma (EC) cells have the characteristics of both stem cells and cancer cells and thus they might be the better candidates for elucidating the details of the reprogramming process. Although previous studies indicate that EC cells cannot be reprogrammed into real pluripotent stem cells, the reasons for this remain unclear. Here, nuclei from mouse EC cells (P19) were transplanted into enucleated oocytes and pluripotent stem cells (P19 NTES cells) were subsequently established. Interestingly, P19 NTES cells prolonged the development of tetraploid aggregated embryos compared to EC cells alone. More importantly, we found that the expression recovery of the imprinted H19 gene was dependent on the methylation state in the differential methylation region (DMR). The induction of Nanog expression, however, was independent of the promoter region DNA methylation state in P19 NTES cells. A whole-genome transcriptome analysis further demonstrated that P19 NTES cells were indeed the intermediates between P19 cells and ES cells and many interesting genes were uncovered that may be responsible for the failed reprogramming of P19 cells. To our knowledge, for the first time, we linked incomplete reprogramming to the improved pluripotency of EC cell-derived pluripotent stem cells. The candidate genes we discovered may be useful not only for understanding the mechanisms of reprogramming, but also for deciphering the transition between tumorigenesis and pluripotency.

Urban rail transit vehicles have been more and more attractive to people as a kind of fast, comfortable, energy-saving, environmental protection and safe transportation. But because of the vehicle noise and vibration, urban rail vehicles also face severe challenges. The research of resilient wheels has been continuously developed and improved. Based on the review of development background and structure sorts of resilient wheels, the advantages of resilient wheels are described, and the research status of noise and vibration reducing, infinite element strength analysis, vehicle dynamic analysis and the wheel-rail wear of resilient wheels are discussed. Taking the low-floor LRVs (light rail vehicles) in domestic and overseas as example, the development and application of the resilient wheels in city rail transit is described, and the application prospects of the resilient wheels in LRVs in domestic and the future research direction of elastic wheel are discussed.