22 results on '"Weissman, Irving L."'
Search Results
2. Dysregulated Gene Expression Networks in Human Acute Myelogenous Leukemia Stem Cells
- Author
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Majeti, Ravindra, Becker, Michael W., Tian, Qiang, Lee, Tsung-Lu Michael, Yan, Xiaowei, Liu, Rui, Chiang, Jung-Hsien, Hood, Leroy, Clarke, Michael F., and Weissman, Irving L.
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- 2009
- Full Text
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3. Epigenetic Characterization of Hematopoietic Stem Cell Differentiation Using MiniChIP and Bisulfite Sequencing Analysis
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Attema, Joanne L., Papathanasiou, Peter, Forsberg, E. Camilla, Xu, Jian, Smale, Stephen T., and Weissman, Irving L.
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- 2007
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4. Ageing hallmarks exhibit organ-specific temporal signatures
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Schaum, Nicholas, Lehallier, Benoit, Hahn, Oliver, Pálovics, Róbert, Hosseinzadeh, Shayan, Lee, Song E., Sit, Rene, Lee, Davis P., Losada, Patricia Morán, Zardeneta, Macy E., Fehlmann, Tobias, Webber, James T., McGeever, Aaron, Calcuttawala, Kruti, Zhang, Hui, Berdnik, Daniela, Mathur, Vidhu, Tan, Weilun, Zee, Alexander, Tan, Michelle, Almanzar, Nicole, Antony, Jane, Baghel, Ankit S., Bakerman, Isaac, Bansal, Ishita, Barres, Ben A., Beachy, Philip A., Bilen, Biter, Brownfield, Douglas, Cain, Corey, Chan, Charles K. F., Chen, Michelle B., Clarke, Michael F., Conley, Stephanie D., Darmanis, Spyros, Demers, Aaron, Demir, Kubilay, de Morree, Antoine, Divita, Tessa, du Bois, Haley, Ebadi, Hamid, Espinoza, F. Hernán, Fish, Matt, Gan, Qiang, George, Benson M., Gillich, Astrid, Gòmez-Sjöberg, Rafael, Green, Foad, Genetiano, Geraldine, Gu, Xueying, Gulati, Gunsagar S., Haney, Michael Seamus, Hang, Yan, Harris, Lincoln, He, Mu, Huang, Albin, Huang, Kerwyn Casey, Iram, Tal, Isobe, Taichi, Ives, Feather, Jones, Robert, Kao, Kevin S., Karkanias, Jim, Karnam, Guruswamy, Keller, Andreas, Kershner, Aaron M., Khoury, Nathalie, Kim, Seung K., Kiss, Bernhard M., Kong, William, Krasnow, Mark A., Kumar, Maya E., Kuo, Christin S., Lam, Jonathan Y., Leventhal, Olivia, Li, Guang, Li, Qingyun, Liu, Ling, Lo, Annie, Lu, Wan-Jin, Lugo-Fagundo, Maria F., Manjunath, Anoop, May, Andrew P., Maynard, Ashley, McKay, Marina, McNerney, M. Windy, Merrill, Bryan, Metzger, Ross J., Mignardi, Marco, Min, Dullei, Nabhan, Ahmad N., Neff, Norma F., Ng, Katharine M., Nguyen, Patricia K., Noh, Joseph, Nusse, Roel, Patkar, Rasika, Peng, Weng Chuan, Penland, Lolita, Pisco, Angela Oliveira, Pollard, Katherine, Puccinelli, Robert, Qi, Zhen, Quake, Stephen R., Rando, Thomas A., Rulifson, Eric J., Segal, Joe M., Sikandar, Shaheen S., Sinha, Rahul, Sonnenburg, Justin, Staehli, Daniel, Szade, Krzysztof, Tato, Cristina, Tellez, Krissie, Torrez Dulgeroff, Laughing Bear, Travaglini, Kyle J., Tropini, Carolina, Tsui, Margaret, Waldburger, Lucas, Wang, Bruce M., van Weele, Linda J., Weinberg, Kenneth, Weissman, Irving L., Wosczyna, Michael N., Wu, Sean M., Wyss-Coray, Tony, Xiang, Jinyi, Xue, Soso, Yamauchi, Kevin A., Yang, Andrew C., Yerra, Lakshmi P., Youngyunpipatkul, Justin, Yu, Brian, Zanini, Fabio, Zhao, Chunyu, Zhang, Fan, Zhang, Martin Jinye, Zhou, Lu, and Zou, James
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0301 basic medicine ,Male ,Aging ,Time Factors ,T-Lymphocytes ,Plasma Cells ,RNA-Seq ,Biology ,Article ,Transcriptome ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Gene expression ,Animals ,RNA, Messenger ,Gene ,Regulation of gene expression ,Multidisciplinary ,Blood Proteins ,Cell biology ,030104 developmental biology ,Proteostasis ,Gene Expression Regulation ,Ageing ,Organ Specificity ,Immunoglobulin J-Chains ,Unfolded protein binding ,Female ,Single-Cell Analysis ,030217 neurology & neurosurgery - Abstract
Ageing is the single greatest cause of disease and death worldwide, and understanding the associated processes could vastly improve quality of life. Although major categories of ageing damage have been identified—such as altered intercellular communication, loss of proteostasis and eroded mitochondrial function1—these deleterious processes interact with extraordinary complexity within and between organs, and a comprehensive, whole-organism analysis of ageing dynamics has been lacking. Here we performed bulk RNA sequencing of 17 organs and plasma proteomics at 10 ages across the lifespan of Mus musculus, and integrated these findings with data from the accompanying Tabula Muris Senis2—or ‘Mouse Ageing Cell Atlas’—which follows on from the original Tabula Muris3. We reveal linear and nonlinear shifts in gene expression during ageing, with the associated genes clustered in consistent trajectory groups with coherent biological functions—including extracellular matrix regulation, unfolded protein binding, mitochondrial function, and inflammatory and immune response. Notably, these gene sets show similar expression across tissues, differing only in the amplitude and the age of onset of expression. Widespread activation of immune cells is especially pronounced, and is first detectable in white adipose depots during middle age. Single-cell RNA sequencing confirms the accumulation of T cells and B cells in adipose tissue—including plasma cells that express immunoglobulin J—which also accrue concurrently across diverse organs. Finally, we show how gene expression shifts in distinct tissues are highly correlated with corresponding protein levels in plasma, thus potentially contributing to the ageing of the systemic circulation. Together, these data demonstrate a similar yet asynchronous inter- and intra-organ progression of ageing, providing a foundation from which to track systemic sources of declining health at old age. Bulk RNA sequencing of organs and plasma proteomics at different ages across the mouse lifespan is integrated with data from the Tabula Muris Senis, a transcriptomic atlas of ageing mouse tissues, to describe organ-specific changes in gene expression during ageing.
- Published
- 2020
5. Hematopoietic stem cells: Expression profiling and beyond
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Forsberg, E. Camilla, Bhattacharya, Deepta, and Weissman, Irving L.
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- 2006
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6. Screening for genes that regulate the differentiation of human megakaryocytic lineage cells.
- Author
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Fangfang Zhu, Mingye Feng, Rahul Sinha, Jun Seita, Yasuo Mori, and Weissman, Irving L.
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TRANSCRIPTION factors ,HEMATOPOIESIS ,GENE expression ,MEGAKARYOCYTES ,HEMATOPOIETIC stem cells ,PROGENITOR cells - Abstract
Different combinations of transcription factors (TFs) function at each stage of hematopoiesis, leading to distinct expression patterns of lineage-specific genes. The identification of such regulators and their functions in hematopoiesis remain largely unresolved. In this study, we utilized screening approaches to study the transcriptional regulators of megakaryocyte progenitor (MkP) generation, a key step before platelet production. Promising candidate genes were generated from a microarray platform gene expression commons and individually manipulated in human hematopoietic stem and progenitor cells (HSPCs). Deletion of some of the candidate genes (the hit genes) by CRISPR/Cas9 led to decreased MkP generation during HSPC differentiation, while more MkPs were produced when some hit genes were overexpressed in HSPCs.We then demonstrated that overexpression of these genes can increase the frequency of mature megakaryocytic colonies by functional colony forming unitmegakaryocyte (CFU-Mk) assay and the release of platelets after in vitro maturation. Finally, we showed that the histone deacetylase inhibitors could also increase MkP differentiation, possibly by regulating some of the newly identified TFs. Therefore, identification of such regulators will advance the understanding of basic mechanisms of HSPC differentiation and conceivably enable the generation and maturation of megakaryocytes and platelets in vitro. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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7. Gene Expression Commons: An Open Platform for Absolute Gene Expression Profiling.
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Seita, Jun, Sahoo, Debashis, Rossi, Derrick J., Bhattacharya, Deepta, Serwold, Thomas, Inlay, Matthew A., Ehrlich, Lauren I. R., Fathman, John W., Dill, David L., and Weissman, Irving L.
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GENE expression ,CELL proliferation ,GENES ,HEREDITY ,MOLECULAR genetics - Abstract
Gene expression profiling using microarrays has been limited to comparisons of gene expression between small numbers of samples within individual experiments. However, the unknown and variable sensitivities of each probeset have rendered the absolute expression of any given gene nearly impossible to estimate. We have overcome this limitation by using a very large number (>10,000) of varied microarray data as a common reference, so that statistical attributes of each probeset, such as the dynamic range and threshold between low and high expression, can be reliably discovered through metaanalysis. This strategy is implemented in a web-based platform named "Gene Expression Commons" (https://gexc.stanford. edu/) which contains data of 39 distinct highly purified mouse hematopoietic stem/progenitor/differentiated cell populations covering almost the entire hematopoietic system. Since the Gene Expression Commons is designed as an open platform, investigators can explore the expression level of any gene, search by expression patterns of interest, submit their own microarray data, and design their own working models representing biological relationship among samples. [ABSTRACT FROM AUTHOR]
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- 2012
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8. Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age.
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Pang, Wendy W., Price, Elizabeth A., Sahoo, Debashis, Beerman, Isabel, Maloney, William J., Rossi, Derrick J., Schrier, Stanley L., and Weissman, Irving L.
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BONE marrow ,BONE marrow cells ,HEMATOPOIETIC stem cells ,GENE expression ,STEM cells - Abstract
In the human hematopoietic system, aging is associated with decreased bone marrow cellularity, decreased adaptive immune system function, and increased incidence of anemia and other hematological disorders and malignancies. Recent studies in mice suggest that changes within the hematopoietic stem cell (HSC) population during aging contribute significantly to the manifestation of these age-associated hematopoietic pathologies. Though the mouse HSC population has been shown to change both quantitatively and functionally with age, changes in the human HSC and progenitor cell populations during aging have been incompletely characterized. To elucidate the properties of an aged human hematopoietic system that may predispose to age-associated hematopoietic dysfunction, we evaluated immunophenotypic HSC and other hematopoietic progenitor populations from healthy, hematologically normal young and elderly human bone marrow samples. We found that aged immunophenotypic human HSC increase in frequency, are less quiescent, and exhibit myeloid-biased differentiation potential compared with young HSC. Gene expression profiling revealed that aged immunophenotypic human HSC transcriptionally up-regulate genes associated with cell cycle, myeloid lineage specification, and myeloid malignancies. These age-associated alterations in the frequency, developmental potential, and gene expression profile of human HSC are similar to those changes observed in mouse HSC, suggesting that hematopoietic aging is an evolutionarily conserved process. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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9. Overexpression of BCL2 enhances survival of human embryonic stem cells during stress and obviates the requirement for serum factors.
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Ardehali, Reza, Inlay, Matthew A., Ali, Shah R., Tang, Chad, Drukker, Micha, and Weissman, Irving L.
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EMBRYONIC stem cells ,CELL culture ,CELL communication ,CELL differentiation ,APOPTOSIS ,GENE expression ,HUMAN genetics - Abstract
The promise of pluripotent stem cells as a research and therapeutic tool is partly undermined by the technical challenges of generating and maintaining these cells in culture. Human embryonic stem cells (hESCs) are exquisitely sensitive to culture conditions, and require constant signaling by growth factors and cell-cell and cell-matrix interactions to prevent apoptosis, senescence, and differentiation. Previous work from our laboratory demonstrated that overexpression of the prosurvival gene BCL2 in mouse embryonic stem cells overrode the requirement of serum factors and feeder cells to maintain mESCs in culture. To determine whether this prosurvival gene could similarly protect hESCs, we generated hESC lines that constitutively or inducibly express BCL2. We find that BCL2 overexpression significantly decreases dissociation-induced apoptosis, resulting in enhanced colony formation from sorted single cells, and enhanced embryoid body formation. In addition, BCL2-hESCs exhibit normal growth in the absence of serum, but require basic fibroblast growth factor to remain undifferentiated. Furthermore, they maintain their pluripotency markers, form teratomas in vivo, and differentiate into all three germ layers. Our data suggest that the BCL2 signaling pathway plays an important role in inhibiting hESC apoptosis, such that its overexpression in hESCs offers both a survival benefit in conditions of stress by resisting apoptosis and obviates the requirement for serum or a feeder layer for maintenance. [ABSTRACT FROM AUTHOR]
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- 2011
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10. Comprehensive methylome map of lineage commitment from haematopoietic progenitors.
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Hong Ji, Lauren I. R.6Ehrlich, Seita, Jun, Murakami, Peter, Doi, Akiko, Lindau, Paul, Hwajin Lee, Aryee, Martin J., Irizarry, Rafael A., Kim, Kitai, Rossi, Derrick J., Inlay, Matthew A., Serwold, Thomas, Karsunky, Holger, Ho, Lena, Daley, George Q., Weissman, Irving L., and Feinberg, Andrew P.
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CELL determination ,CELL differentiation ,NUCLEOTIDE sequence ,METHYLTRANSFERASES ,TRANSCRIPTION factors ,GENE expression - Abstract
Epigenetic modifications must underlie lineage-specific differentiation as terminally differentiated cells express tissue-specific genes, but their DNA sequence is unchanged. Haematopoiesis provides a well-defined model to study epigenetic modifications during cell-fate decisions, as multipotent progenitors (MPPs) differentiate into progressively restricted myeloid or lymphoid progenitors. Although DNA methylation is critical for myeloid versus lymphoid differentiation, as demonstrated by the myeloerythroid bias in Dnmt1 hypomorphs, a comprehensive DNA methylation map of haematopoietic progenitors, or of any multipotent/oligopotent lineage, does not exist. Here we examined 4.6 million CpG sites throughout the genome for MPPs, common lymphoid progenitors (CLPs), common myeloid progenitors (CMPs), granulocyte/macrophage progenitors (GMPs), and thymocyte progenitors (DN1, DN2, DN3). Marked epigenetic plasticity accompanied both lymphoid and myeloid restriction. Myeloid commitment involved less global DNA methylation than lymphoid commitment, supported functionally by myeloid skewing of progenitors following treatment with a DNA methyltransferase inhibitor. Differential DNA methylation correlated with gene expression more strongly at CpG island shores than CpG islands. Many examples of genes and pathways not previously known to be involved in choice between lymphoid/myeloid differentiation have been identified, such as Arl4c and Jdp2. Several transcription factors, including Meis1, were methylated and silenced during differentiation, indicating a role in maintaining an undifferentiated state. Additionally, epigenetic modification of modifiers of the epigenome seems to be important in haematopoietic differentiation. Our results directly demonstrate that modulation of DNA methylation occurs during lineage-specific differentiation and defines a comprehensive map of the methylation and transcriptional changes that accompany myeloid versus lymphoid fate decisions. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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11. Distinguishing Mast Cell and Granulocyte Differentiation at the Single–Cell Level.
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Franco, Christopher B., Ching-Cheng Chen, Drukker, Micha, Weissman, Irving L., and GaIIi, Stephen J.
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MAST cells ,GRANULOCYTES ,MEGAKARYOCYTES ,HEMATOPOIESIS ,ERYTHROCYTES ,GENE expression - Abstract
The lineage restriction of prospectively, isolated hematopoietic progenitors has been traditionally assessed by bulk in vitro culture and transplantation of large number of cells in vivo. These methods, however, cannot distinguish between homogenous mul–tipotent or heterogeneous lineage–restricted populations. Using clonal assays of 1 or 5 cells in vitro, single–cell quantitative gene expression analyses, and transplantation of mice with low numbers of cells, we show that a common myeloid progenitor (CMP) is Sca–
lo lin- c–Kit'CD27+ Flk–2- (SL–CMP; Sca–1lo CMP) and a granulocyte/macrophage progenitor (GMP) is Sca-1lo lin- c–Kit+ CD27+ Flk–2+ CD150- /lo (SL– GMP; Sca–1lo GMP). We found that mast cell progenitor potential is present in the SL – CMP fraction, but not in the more differentiated SL-GMP population, and is more closely related to megakaryocyte/erythrocyte specification. Our data provide criteria for the prospective isolation of SL – CMP and SL– GMP and support the conclusion that mast cells are specified during hematopoiesis earlier than and independently from granulocytes. [ABSTRACT FROM AUTHOR]- Published
- 2010
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12. MiDReG: A method of mining developmentally regulated genes using Boolean implications.
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Sahoo, Debashis, Seita, Jun, Bhattacharya, Deepta, Inlay, Matthew A., Weissman, Irving L., Plevritis, Sylvia K., and DiIl, David L.
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GENETIC regulation ,B cell differentiation ,MOLECULAR genetics ,DNA microarrays ,PROTEIN microarrays ,GENE amplification - Abstract
We present a method termed mining developmentally regulated genes (MiDReG) to predict genes whose expression is either activated or repressed as precursor cells differentiate. MiDReG does not require gene expression data from intermediate stages of development. MiDReG is based on the gene expression patterns between the initial and terminal stages of the differentiation pathway. coupled with "if-then" rules (Boolean implications) mined from large-scale microarray databases. MiDReG uses two gene expression-based seed conditions that mark the initial and the terminal stages of a given differentiation pathway and combines the statistically inferred Boolean implications from these seed conditions to identify the relevant genes. The method was validated by applying it to B-cell development. The algorithm pçedicted 62 genes that are expressed after the KIT+ progenitor cell stage and remain expressed through CD19+ and AICDA+ germinal center B cells. qRT-PCR of 14 of these genes on sorted B-cell progenitors confirmed that the expression of 10 genes is indeed stably established during B-cell differentiation. Review of the published literature of knockout mice revealed that of the predicted genes, 63.4% have defects in B-cell differentiation and function and 22% have a role in the B cell according to other experiments, and the remaining 14.6% are not characterized. Therefore, our method identified novel gene candidates for future examination of their role in B-cell development. These data demonstrate the power of MiDReG in predicting functionally important intermediate genes in a given developmental pathway that is defined by a mutually exclusive gene expression pattern. [ABSTRACT FROM AUTHOR]
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- 2010
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13. Molecular Signatures of Quiescent, Mobilized and Leukemia-Initiating Hematopoietic Stem Cells.
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Forsberg, E. Camilla, Passegué, Emmanuelle, Prohaska, Susan S., Wagers, Amy J., Koeva, Martina, Stuart, Joshua M., and Weissman, Irving L.
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HEMATOPOIETIC stem cells ,BONE marrow cells ,PRELEUKEMIA ,BLOOD cells ,IMMUNE system ,GENETIC regulation ,GENE expression ,ANATMAN ,STEM cells - Abstract
Hematopoietic stem cells (HSC) are rare, multipotent cells capable of generating all specialized cells of the blood system. Appropriate regulation of HSC quiescence is thought to be crucial to maintain their lifelong function; however, the molecular pathways controlling stem cell quiescence remain poorly characterized. Likewise, the molecular events driving leukemogenesis remain elusive. In this study, we compare the gene expression profiles of steady-state bone marrow HSC to non-self-renewing multipotent progenitors; to HSC treated with mobilizing drugs that expand the HSC pool and induce egress from the marrow; and to leukemic HSC in a mouse model of chronic myelogenous leukemia. By intersecting the resulting lists of differentially regulated genes we identify a subset of molecules that are downregulated in all three circumstances, and thus may be particularly important for the maintenance and function of normal, quiescent HSC. These results identify potential key regulators of HSC and give insights into the clinically important processes of HSC mobilization for transplantation and leukemic development from cancer stem cells. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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- View/download PDF
14. Cancer stem cells in solid tumors
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Ailles, Laurie E and Weissman, Irving L
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CANCER cells , *STEM cells , *CARCINOGENESIS , *TUMORS , *BREAST cancer , *GENE expression , *PROGNOSIS - Abstract
Cancer stem cells (CSCs) are cells that drive tumorigenesis, as well as giving rise to a large population of differentiated progeny that make up the bulk of the tumor, but that lack tumorigenic potential. CSCs have been identified in a variety of human tumors, as assayed by their ability to initiate tumor growth in immunocompromised mice. Further characterization studies have demonstrated that gene expression profiles in breast cancer correlate with patient prognosis, and brain CSCs are specifically resistant to radiation through DNA damage repair. In addition, specific signaling pathways play a functional role in CSC self renewal and/or differentiation, and early studies indicate that CSCs are associated with a microenvironmental niche. Thus the biological properties of CSCs are just beginning to be revealed, and the continuation of these studies should lead to the development of CSC-targeted therapies for cancer treatment. [Copyright &y& Elsevier]
- Published
- 2007
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15. Memory T and memory B cells share a transcriptional program of self-renewal with long-term hematopoletic stem cells.
- Author
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Luckey, Chance John, Bhattacharya, Deepta, GoIdrath, Ananda W., Weissman, Irving L., Benoist, Christophe, and Mathis, Diane
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T cells ,B cells ,GENETIC transcription ,HEMATOPOIETIC stem cells ,GENE expression ,PLASMA cells ,EMBRYONIC stem cells ,HEMATOPOIETIC system ,GENOTYPE-environment interaction - Abstract
The only cells of the hematopoietic system that undergo self-renewal for the lifetime of the organism are long-term hematopoietic stem cells and memory T and B cells. To determine whether there is a shared transcriptional program among these self-renewing populations, we first compared the gene-expression profiles of naïve, effector and memory CD8
+ T cells with those of long-term hematopoietic stem cells, short-term hematopoietic stem cells, and lineage-committed progenitors. Transcripts augmented in memory CD8+ T cells relative to naïve and effector T cells were selectively enriched in long-term hematopoietic stem cells and were progressively lost in their short-term and lineage-committed counterparts. Furthermore, transcripts selectively decreased in memory CD8+ T cells were selectively down-regulated in long-term hematopoietic stem cells and progressively increased with differentiation. To confirm that this pattern was a general property of immunologic memory, we turned to independently generated gene expression profiles of memory, naïve, germinal center, and plasma B cells. Once again, memory-enriched and -depleted transcripts were also appropriately augmented and diminished in long-term hematopoietic stem cells, and their expression correlated with progressive loss of self-renewal function. Thus, there appears to be a common signature of both up- and down-regulated transcripts shared between memory T cells, memory B cells, and long-term hematopoietic stem cells. This signature was not consistently enriched in neural or embryonic stem cell populations and, therefore, appears to be restricted to the hematopoeitic system. These observations provide evidence that the shared phenotype of self-renewal in the hematopoietic system is linked at the molecular level. [ABSTRACT FROM AUTHOR]- Published
- 2006
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16. Cell intrinsic alterations underlie hematopoietic stem cell aging.
- Author
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Rossi, Derrick J., Bryder, David, Zahn, Jacob M., Ahlenius, Henrik, Sonu, Rebecca, Wagers, Amy J., and Weissman, Irving L.
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STEM cells ,MYELOID leukemia ,GENE expression ,LABORATORY mice ,LYMPHOID tissue ,IMMUNE system - Abstract
Loss of immune function and an increased incidence of myeloid leukemia are two of the most clinically significant consequences of aging of the hematopoietic system. To better understand the mechanisms underlying hematopoietic aging, we evaluated the cell intrinsic functional and molecular properties of highly purified long-term hematopoietic stem cells (LT-HSCs) from young and old mice. We found that LT-HSC aging was accompanied by cell autonomous changes, including increased stem cell self-renewal, differential capacity to generate committed myeloid and lymphoid progenitors, and diminished lymphoid potential. Expression profiling revealed that LT-HSC aging was accompanied by the systemic down-regulation of genes mediating lymphoid specification and function and up-regulation of genes involved in specifying myeloid fate and function. Moreover, LT-HSCs from old mice expressed elevated levels of many genes involved in leukemic transformation. These data support a model in which age-dependent alterations in gene expression at the stem cell level presage downstream developmental potential and thereby contribute to age-dependent immune decline, and perhaps also to the increased incidence of leukemia in the elderly. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
17. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells.
- Author
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Park, In-kyung, Qian, Dalong, Kiel, Mark, Becker, Michael W., Pihalja, Michael, Weissman, Irving L., Morrison, Sean J., and Clarke, Michael F.
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HEMATOPOIETIC stem cells ,GENE expression ,TRANSCRIPTION factors ,CELL death - Abstract
A central issue in stem cell biology is to understand the mechanisms that regulate the self-renewal of haematopoietic stem cells (HSCs), which are required for haematopoiesis to persist for the lifetime of the animal. We found that adult and fetal mouse and adult human HSCs express the proto-oncogene Bmi-1. The number of HSCs in the fetal liver of Bmi-1
-/- mice was normal. In postnatal Bmi-1-/- mice, the number of HSCs was markedly reduced. Transplanted fetal liver and bone marrow cells obtained from Bmi-1-/- mice were able to contribute only transiently to haematopoiesis. There was no detectable self-renewal of adult HSCs, indicating a cell autonomous defect in Bmi-1-/- mice. A gene expression analysis revealed that the expression of stem cell associated genes, cell survival genes, transcription factors, and genes modulating proliferation including p16Ink4a and p19Arf was altered in bone marrow cells of the Bmi-1-/- mice. Expression of p16Ink4a and p19Arf in normal HSCs resulted in proliferative arrest and p53-dependent cell death, respectively. Our results indicate that Bmi-1 is essential for the generation of self-renewing adult HSCs. [ABSTRACT FROM AUTHOR]- Published
- 2003
- Full Text
- View/download PDF
18. AML1-ETO expression is directly involved development of acute myeloid leukemia in the presence....
- Author
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Youzhong Yuan, Liming Zhou, Miyamoto, Toshihiro, Iwasaki, Hiromi, Harakawa, Nari, Hetherington, Christopher J., Burel, Sebastien A., Lagasse, Eric, Weissman, Irving L., Akashi, Koichi, and Dong-Er Zhang
- Subjects
GENE expression ,MYELOID leukemia ,FLOW cytometry - Abstract
Examines the involvement of ETO gene expression in the development of acute myeloid leukemia. Myeloid specific expression of AML-ETO gene in transgenic mice; Normality of hematopoiesis; Induction of Western blot analysis and flow cytometry for the investigation.
- Published
- 2001
- Full Text
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19. From hematopoiesis to neuropoiesis: Evidence of overlapping genetic programs.
- Author
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Terskikh, Alexey V., Easterday, Mathew C., Linheng Li, Hood, Leroy, Kornblum, Harley I., Geschwind, Daniel H., and Weissman, Irving L.
- Subjects
GENE expression ,STEM cells - Abstract
Examines the gene expression of purified stem cells for the molecular mechanism of stem cell behavior. Identification of gene from hematopoietic stem cells of mouse; Advantages of complementary DNA for gene identification; Differentiation of genes from hematopoiesis to neuropoiesis.
- Published
- 2001
- Full Text
- View/download PDF
20. Neural progenitor genes: Germinal zone expression and analysis of genetic overlap in stem cell populations
- Author
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Easterday, Mathew C., Dougherty, Joseph D., Jackson, Robert L., Ou, Jing, Nakano, Ichiro, Paucar, Andres A., Roobini, Babak, Dianati, Mehrnoosh, Irvin, Dwain K., Weissman, Irving L., Terskikh, Alexey V., Geschwind, Daniel H., and Kornblum, Harley I.
- Subjects
- *
GENES , *NEUROSCIENCES , *GENE expression , *STEM cells - Abstract
The identification of the genes regulating neural progenitor cell (NPC) functions is of great importance to developmental neuroscience and neural repair. Previously, we combined genetic subtraction and microarray analysis to identify genes enriched in neural progenitor cultures. Here, we apply a strategy to further stratify the neural progenitor genes. In situ hybridization demonstrates expression in the central nervous system germinal zones of 54 clones so identified, making them highly relevant for study in brain and neural progenitor development. Using microarray analysis we find 73 genes enriched in three neural stem cell (NSC)-containing populations generated under different conditions. We use the custom microarray to identify 38 “stemness” genes, with enriched expression in the three NSC conditions and present in both embryonic stem cells and hematopoietic stem cells. However, comparison of expression profiles from these stem cell populations indicates that while there is shared gene expression, the amount of genetic overlap is no more than what would be expected by chance, indicating that different stem cells have largely different gene expression patterns. Taken together, these studies identify many genes not previously associated with neural progenitor cell biology and also provide a rational scheme for stratification of microarray data for functional analysis. [Copyright &y& Elsevier]
- Published
- 2003
- Full Text
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21. Myeloid or Lymphoid Promiscuity as a Critical Step in Hematopoietic Lineage Commitment
- Author
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Miyamoto, Toshihiro, Iwasaki, Hiromi, Reizis, Boris, Ye, Min, Graf, Thomas, Weissman, Irving L., and Akashi, Koichi
- Subjects
- *
HEMATOPOIESIS , *LYMPHOID tissue , *GENE expression - Abstract
We demonstrate here that “promiscuous” expression of myeloid or lymphoid genes precedes lineage commitment in hematopoiesis. Prospectively purified single common myeloid progenitors (CMPs) coexpress myelo-erythroid but not lymphoid genes, whereas single common lymphoid progenitors (CLPs) coexpress T and B lymphoid but not myeloid genes. Genes unrelated to the adopted lineage are downregulated in bipotent and monopotent descendants of CMPs and CLPs. Promiscuous gene expression does not alter the biological potential of multipotent progenitors: CMPs with an activated endogenous M lysozyme locus yield normal proportions of myelo-erythroid colonies, and CLPs expressing the pre-T cell receptor α gene differentiate into normal numbers of B cells. Thus, the accessibility for multiple myeloid or lymphoid programs promiscuously may allow flexibility in fate commitments at these multipotent stages. [Copyright &y& Elsevier]
- Published
- 2002
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22. Engrailed-1 Identifies the Fibroblast Lineage Responsible for the Transition from Fetal Scarless to Adult Scarring Cutaneous Wound Repair.
- Author
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Hu, Michael S., Walmsley, Graham G., Maan, Zeshaan N., Sinha, Rahul, Leavitt, Tripp, Marshall, Clement D., Weissman, Irving L., Gurtner, Geoffrey C., Longaker, Michael T., and Lorenz, H Peter
- Subjects
- *
FIBROBLASTS , *WOUND healing , *SCARS , *EMBRYOLOGY , *GENE expression , *LABORATORY mice , *THERAPEUTICS - Published
- 2016
- Full Text
- View/download PDF
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