The Experts below are selected from a list of 4020 Experts worldwide ranked by ideXlab platform
Shufen Wang - One of the best experts on this subject based on the ideXlab platform.
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A network among TGFβ1/activin/nodal, FGF and Wnt pathways cooperate to Maintain Pluripotency and self-renew of rabbit embryonic stem cells
Cell Research, 2008Co-Authors: Shufen WangAbstract:A network among TGFβ1/activin/nodal, FGF and Wnt pathways cooperate to Maintain Pluripotency and self-renew of rabbit embryonic stem cells
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a network among tgfβ1 activin nodal fgf and wnt pathways cooperate to Maintain Pluripotency and self renew of rabbit embryonic stem cells
Cell Research, 2008Co-Authors: Shufen WangAbstract:A network among TGFβ1/activin/nodal, FGF and Wnt pathways cooperate to Maintain Pluripotency and self-renew of rabbit embryonic stem cells
Roger A. Pedersen - One of the best experts on this subject based on the ideXlab platform.
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activin nodal signaling controls divergent transcriptional networks in human embryonic stem cells and in endoderm progenitors
Stem Cells, 2011Co-Authors: Stephanie Brown, Adrian Kee Keong Teo, Matthew Trotter, Candy H.-h. Cho, Siim Pauklin, Nicholas R F Hannan, Bing Lim, Leah A Vardy, Ray N Dunn, Roger A. PedersenAbstract:Activin/Nodal signaling is necessary to Maintain Pluripotency of human embryonic stem cells (hESCs) and to induce their differentiation toward endoderm. However, the mechanisms by which Activin/Nodal signaling achieves these opposite functions remain unclear. To unravel these mechanisms, we examined the transcriptional network controlled in hESCs by Smad2 and Smad3, which represent the direct effectors of Activin/Nodal signaling. These analyses reveal that Smad2/3 participate in the control of the core transcriptional network characterizing Pluripotency, which includes Oct-4, Nanog, FoxD3, Dppa4, Tert, Myc, and UTF1. In addition, similar experiments performed on endoderm cells confirm that a broad part of the transcriptional network directing differentiation is downstream of Smad2/3. Therefore, Activin/Nodal signaling appears to control divergent transcriptional networks in hESCs and in endoderm. Importantly, we observed an overlap between the transcriptional network downstream of Nanog and Smad2/3 in hESCs; whereas, functional studies showed that both factors cooperate to control the expression of Pluripotency genes. Therefore, the effect of Activin/Nodal signaling on Pluripotency and differentiation could be dictated by tissue specific Smad2/3 partners such as Nanog, explaining the mechanisms by which signaling pathways can orchestrate divergent cell fate decisions. STEM CELLS 2011;29:1176–1185
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Activin/Nodal and FGF pathways cooperate to Maintain Pluripotency of human embryonic stem cells.
Journal of cell science, 2005Co-Authors: Ludovic Vallier, Morgan Alexander, Roger A. PedersenAbstract:Maintenance of Pluripotency is crucial to the mammalian embryo's ability to generate the extra-embryonic and embryonic tissues that are needed for intrauterine survival and foetal development. The recent establishment of embryonic stem cells from human blastocysts (hESCs) provides an opportunity to identify the factors supporting Pluripotency at early stages of human development. Using this in vitro model, we have recently shown that Nodal can block neuronal differentiation, suggesting that TGFbeta family members are involved in cell fate decisions of hESCs, including preservation of their Pluripotency. Here, we report that Activin/Nodal signalling through Smad2/3 activation is necessary to Maintain the pluripotent status of hESCs. Inhibition of Activin/Nodal signalling by follistatin and by overexpression of Lefty or Cerberus-Short, or by the Activin receptor inhibitor SB431542, precipitates hESC differentiation. Nevertheless, neither Nodal nor Activin is sufficient to sustain long-term hESC growth in a chemically defined medium without serum. Recent studies have shown that FGF2 can also Maintain long-term expression of Pluripotency markers, and we find that inhibition of the FGF signalling pathway by the tyrosine kinase inhibitor SU5402 causes hESC differentiation. However, this effect of FGF on hESC Pluripotency depends on Activin/Nodal signalling, because it is blocked by SB431542. Finally, long-term maintenance of in-vitro Pluripotency can be achieved with a combination of Activin or Nodal plus FGF2 in the absence of feeder-cell layers, conditioned medium or Serum Replacer. These findings suggest that the Activin/Nodal pathway Maintains Pluripotency through mechanism(s) in which FGF acts as a competence factor and therefore provide further evidence of distinct mechanisms for preservation of Pluripotency in mouse and human ESCs.
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activin nodal and fgf pathways cooperate to Maintain Pluripotency of human embryonic stem cells
Journal of Cell Science, 2005Co-Authors: Ludovic Vallier, Morgan Alexander, Roger A. PedersenAbstract:Maintenance of Pluripotency is crucial to the mammalian embryo's ability to generate the extra-embryonic and embryonic tissues that are needed for intrauterine survival and foetal development. The recent establishment of embryonic stem cells from human blastocysts (hESCs) provides an opportunity to identify the factors supporting Pluripotency at early stages of human development. Using this in vitro model, we have recently shown that Nodal can block neuronal differentiation, suggesting that TGFβ family members are involved in cell fate decisions of hESCs, including preservation of their Pluripotency. Here, we report that Activin/Nodal signalling through Smad2/3 activation is necessary to Maintain the pluripotent status of hESCs. Inhibition of Activin/Nodal signalling by follistatin and by overexpression of Lefty or Cerberus-Short, or by the Activin receptor inhibitor SB431542, precipitates hESC differentiation. Nevertheless, neither Nodal nor Activin is sufficient to sustain long-term hESC growth in a chemically defined medium without serum. Recent studies have shown that FGF2 can also Maintain long-term expression of Pluripotency markers, and we find that inhibition of the FGF signalling pathway by the tyrosine kinase inhibitor SU5402 causes hESC differentiation. However, this effect of FGF on hESC Pluripotency depends on Activin/Nodal signalling, because it is blocked by SB431542. Finally, long-term maintenance of in-vitro Pluripotency can be achieved with a combination of Activin or Nodal plus FGF2 in the absence of feeder-cell layers, conditioned medium or Serum Replacer. These findings suggest that the Activin/Nodal pathway Maintains Pluripotency through mechanism(s) in which FGF acts as a competence factor and therefore provide further evidence of distinct mechanisms for preservation of Pluripotency in mouse and human ESCs.
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Activin/Nodal and FGF pathways cooperate to Maintain Pluripotency of human embryonic stem cells.
Journal of Cell Science, 2005Co-Authors: Ludovic Vallier, Morgan Alexander, Roger A. PedersenAbstract:Maintenance of Pluripotency is crucial to the mammalian embryo's ability to generate the extra-embryonic and embryonic tissues that are needed for intrauterine survival and foetal development. The recent establishment of embryonic stem cells from human blastocysts (hESCs) provides an opportunity to identify the factors supporting Pluripotency at early stages of human development. Using this in vitro model, we have recently shown that Nodal can block neuronal differentiation, suggesting that TGFβ family members are involved in cell fate decisions of hESCs, including preservation of their Pluripotency. Here, we report that Activin/Nodal signalling through Smad2/3 activation is necessary to Maintain the pluripotent status of hESCs. Inhibition of Activin/Nodal signalling by follistatin and by overexpression of Lefty or Cerberus-Short, or by the Activin receptor inhibitor SB431542, precipitates hESC differentiation. Nevertheless, neither Nodal nor Activin is sufficient to sustain long-term hESC growth in a chemically defined medium without serum. Recent studies have shown that FGF2 can also Maintain long-term expression of Pluripotency markers, and we find that inhibition of the FGF signalling pathway by the tyrosine kinase inhibitor SU5402 causes hESC differentiation. However, this effect of FGF on hESC Pluripotency depends on Activin/Nodal signalling, because it is blocked by SB431542. Finally, long-term maintenance of in-vitro Pluripotency can be achieved with a combination of Activin or Nodal plus FGF2 in the absence of feeder-cell layers, conditioned medium or Serum Replacer. These findings suggest that the Activin/Nodal pathway Maintains Pluripotency through mechanism(s) in which FGF acts as a competence factor and therefore provide further evidence of distinct mechanisms for preservation of Pluripotency in mouse and human ESCs.
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Human embryonic stem cells
Neurosurgical Focus, 2005Co-Authors: Ludovic Vallier, Roger A. PedersenAbstract:The property of Pluripotency confers the capacity for differentiation into a large number of cell types including extra-embryonic, somatic and germinal cells. During normal development, Pluripotency is acquired by the cells of the early embryo, which shortly thereafter undergo differentiation, whereas embryonic stem cells (ESCs) uniquely Maintain Pluripotency while undergoing extensive in vitro proliferation. Studies using ESCs have begun to unravel the network of cytokines and transcription factors responsible for their maintenance of Pluripotency. Surprisingly, mouse and human ESCs display significant differences in such mechanisms despite their similar embryonic origins. In this review, we compare the properties of pluripotent embryonic cells with those of ESCs to establish a general model for the mechanisms Maintaining Pluripotency. We first consider whether mouse and human ESCs represent comparable stages of early embryonic development. We then describe how human embryoid body (EB) differentiation could be used as a model of embryonic development. Finally, to concretely illustrate the discussion, we discuss our recent results concerning Nodal function in controlling cell fate at early stages of human EB development. With the new perspective of these findings, we suggest a previously unrecognized role of TGF-β pathway signaling in Maintaining Pluripotency at early stages of mammalian embryonic development.
Ludovic Vallier - One of the best experts on this subject based on the ideXlab platform.
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Activin/Nodal signalling Maintains Pluripotency by controlling Nanog expression
Development (Cambridge England), 2009Co-Authors: Ludovic Vallier, Sasha Mendjan, Stephanie Brown, Zhenzhi Chng, Adrian Kee Keong Teo, Lucy E. Smithers, Matthew Trotter, Candy H.-h. Cho, Amelie Martinez, Peter J. Rugg-gunnAbstract:The pluripotent status of embryonic stem cells (ESCs) confers upon them the capacity to differentiate into the three primary germ layers, ectoderm, mesoderm and endoderm, from which all the cells of the adult body are derived. An understanding of the mechanisms controlling Pluripotency is thus essential for driving the differentiation of human pluripotent cells into cell types useful for clinical applications. The Activin/Nodal signalling pathway is necessary to Maintain Pluripotency in human ESCs and in mouse epiblast stem cells (EpiSCs), but the molecular mechanisms by which it achieves this effect remain obscure. Here, we demonstrate that Activin/Nodal signalling controls expression of the key Pluripotency factor Nanog in human ESCs and in mouse EpiSCs. Nanog in turn prevents neuroectoderm differentiation induced by FGF signalling and limits the transcriptional activity of the Smad2/3 cascade, blocking progression along the endoderm lineage. This negative-feedback loop imposes stasis in neuroectoderm and mesendoderm differentiation, thereby Maintaining the pluripotent status of human ESCs and mouse EpiSCs.
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Activin/Nodal and FGF pathways cooperate to Maintain Pluripotency of human embryonic stem cells.
Journal of cell science, 2005Co-Authors: Ludovic Vallier, Morgan Alexander, Roger A. PedersenAbstract:Maintenance of Pluripotency is crucial to the mammalian embryo's ability to generate the extra-embryonic and embryonic tissues that are needed for intrauterine survival and foetal development. The recent establishment of embryonic stem cells from human blastocysts (hESCs) provides an opportunity to identify the factors supporting Pluripotency at early stages of human development. Using this in vitro model, we have recently shown that Nodal can block neuronal differentiation, suggesting that TGFbeta family members are involved in cell fate decisions of hESCs, including preservation of their Pluripotency. Here, we report that Activin/Nodal signalling through Smad2/3 activation is necessary to Maintain the pluripotent status of hESCs. Inhibition of Activin/Nodal signalling by follistatin and by overexpression of Lefty or Cerberus-Short, or by the Activin receptor inhibitor SB431542, precipitates hESC differentiation. Nevertheless, neither Nodal nor Activin is sufficient to sustain long-term hESC growth in a chemically defined medium without serum. Recent studies have shown that FGF2 can also Maintain long-term expression of Pluripotency markers, and we find that inhibition of the FGF signalling pathway by the tyrosine kinase inhibitor SU5402 causes hESC differentiation. However, this effect of FGF on hESC Pluripotency depends on Activin/Nodal signalling, because it is blocked by SB431542. Finally, long-term maintenance of in-vitro Pluripotency can be achieved with a combination of Activin or Nodal plus FGF2 in the absence of feeder-cell layers, conditioned medium or Serum Replacer. These findings suggest that the Activin/Nodal pathway Maintains Pluripotency through mechanism(s) in which FGF acts as a competence factor and therefore provide further evidence of distinct mechanisms for preservation of Pluripotency in mouse and human ESCs.
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activin nodal and fgf pathways cooperate to Maintain Pluripotency of human embryonic stem cells
Journal of Cell Science, 2005Co-Authors: Ludovic Vallier, Morgan Alexander, Roger A. PedersenAbstract:Maintenance of Pluripotency is crucial to the mammalian embryo's ability to generate the extra-embryonic and embryonic tissues that are needed for intrauterine survival and foetal development. The recent establishment of embryonic stem cells from human blastocysts (hESCs) provides an opportunity to identify the factors supporting Pluripotency at early stages of human development. Using this in vitro model, we have recently shown that Nodal can block neuronal differentiation, suggesting that TGFβ family members are involved in cell fate decisions of hESCs, including preservation of their Pluripotency. Here, we report that Activin/Nodal signalling through Smad2/3 activation is necessary to Maintain the pluripotent status of hESCs. Inhibition of Activin/Nodal signalling by follistatin and by overexpression of Lefty or Cerberus-Short, or by the Activin receptor inhibitor SB431542, precipitates hESC differentiation. Nevertheless, neither Nodal nor Activin is sufficient to sustain long-term hESC growth in a chemically defined medium without serum. Recent studies have shown that FGF2 can also Maintain long-term expression of Pluripotency markers, and we find that inhibition of the FGF signalling pathway by the tyrosine kinase inhibitor SU5402 causes hESC differentiation. However, this effect of FGF on hESC Pluripotency depends on Activin/Nodal signalling, because it is blocked by SB431542. Finally, long-term maintenance of in-vitro Pluripotency can be achieved with a combination of Activin or Nodal plus FGF2 in the absence of feeder-cell layers, conditioned medium or Serum Replacer. These findings suggest that the Activin/Nodal pathway Maintains Pluripotency through mechanism(s) in which FGF acts as a competence factor and therefore provide further evidence of distinct mechanisms for preservation of Pluripotency in mouse and human ESCs.
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Activin/Nodal and FGF pathways cooperate to Maintain Pluripotency of human embryonic stem cells.
Journal of Cell Science, 2005Co-Authors: Ludovic Vallier, Morgan Alexander, Roger A. PedersenAbstract:Maintenance of Pluripotency is crucial to the mammalian embryo's ability to generate the extra-embryonic and embryonic tissues that are needed for intrauterine survival and foetal development. The recent establishment of embryonic stem cells from human blastocysts (hESCs) provides an opportunity to identify the factors supporting Pluripotency at early stages of human development. Using this in vitro model, we have recently shown that Nodal can block neuronal differentiation, suggesting that TGFβ family members are involved in cell fate decisions of hESCs, including preservation of their Pluripotency. Here, we report that Activin/Nodal signalling through Smad2/3 activation is necessary to Maintain the pluripotent status of hESCs. Inhibition of Activin/Nodal signalling by follistatin and by overexpression of Lefty or Cerberus-Short, or by the Activin receptor inhibitor SB431542, precipitates hESC differentiation. Nevertheless, neither Nodal nor Activin is sufficient to sustain long-term hESC growth in a chemically defined medium without serum. Recent studies have shown that FGF2 can also Maintain long-term expression of Pluripotency markers, and we find that inhibition of the FGF signalling pathway by the tyrosine kinase inhibitor SU5402 causes hESC differentiation. However, this effect of FGF on hESC Pluripotency depends on Activin/Nodal signalling, because it is blocked by SB431542. Finally, long-term maintenance of in-vitro Pluripotency can be achieved with a combination of Activin or Nodal plus FGF2 in the absence of feeder-cell layers, conditioned medium or Serum Replacer. These findings suggest that the Activin/Nodal pathway Maintains Pluripotency through mechanism(s) in which FGF acts as a competence factor and therefore provide further evidence of distinct mechanisms for preservation of Pluripotency in mouse and human ESCs.
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Human embryonic stem cells
Neurosurgical Focus, 2005Co-Authors: Ludovic Vallier, Roger A. PedersenAbstract:The property of Pluripotency confers the capacity for differentiation into a large number of cell types including extra-embryonic, somatic and germinal cells. During normal development, Pluripotency is acquired by the cells of the early embryo, which shortly thereafter undergo differentiation, whereas embryonic stem cells (ESCs) uniquely Maintain Pluripotency while undergoing extensive in vitro proliferation. Studies using ESCs have begun to unravel the network of cytokines and transcription factors responsible for their maintenance of Pluripotency. Surprisingly, mouse and human ESCs display significant differences in such mechanisms despite their similar embryonic origins. In this review, we compare the properties of pluripotent embryonic cells with those of ESCs to establish a general model for the mechanisms Maintaining Pluripotency. We first consider whether mouse and human ESCs represent comparable stages of early embryonic development. We then describe how human embryoid body (EB) differentiation could be used as a model of embryonic development. Finally, to concretely illustrate the discussion, we discuss our recent results concerning Nodal function in controlling cell fate at early stages of human EB development. With the new perspective of these findings, we suggest a previously unrecognized role of TGF-β pathway signaling in Maintaining Pluripotency at early stages of mammalian embryonic development.
Hitoshi Niwa - One of the best experts on this subject based on the ideXlab platform.
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the Pluripotency transcription factor network at work in reprogramming
Current Opinion in Genetics & Development, 2014Co-Authors: Hitoshi NiwaAbstract:Pluripotency-associated transcription factors possess a pivotal role to Maintain Pluripotency in pluripotent stem cells as well as to induce Pluripotency in somatic cells. They direct specific pattern of gene expression from the genome by co-operating with the genetic and epigenetic mechanisms. Recent findings revealed that these mechanisms possess unique features in pluripotent stem cells, which is different from that in somatic cells either qualitatively and quantitatively. To reprogram somatic cells, Pluripotency-associated transcription factors should modulate the co-operating machineries to establish the optimal environment for their function to Maintain Pluripotency-associated transcription factor network.
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Wnt: what's needed to Maintain Pluripotency?
Nature cell biology, 2011Co-Authors: Hitoshi NiwaAbstract:A precise role for the canonical Wnt pathway in Maintaining Pluripotency in mouse embryonic stem cells (mESCs) has been debated. Four recent reports add pieces to the puzzle and together these results may help establish a robust model.
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A parallel circuit of LIF signalling pathways Maintains Pluripotency of mouse ES cells
Nature, 2009Co-Authors: Hitoshi Niwa, Kazuya Ogawa, Daisuke Shimosato, Kenjiro AdachiAbstract:The cytokine leukaemia inhibitory factor (LIF) integrates signals into mouse embryonic stem (ES) cells to Maintain Pluripotency. Although the Jak-Stat3 pathway is essential and sufficient to mediate LIF signals, it is still unclear how these signals are linked to the core circuitry of Pluripotency-associated transcription factors, consisting of Oct3/4 (also called Pou5f1), Sox2 and Nanog. Here we show that two LIF signalling pathways are each connected to the core circuitry via different transcription factors. In mouse ES cells, Klf4 is mainly activated by the Jak-Stat3 pathway and preferentially activates Sox2, whereas Tbx3 is preferentially regulated by the phosphatidylinositol-3-OH kinase-Akt and mitogen-activated protein kinase pathways and predominantly stimulates Nanog. In the absence of LIF, artificial expression of Klf4 or Tbx3 is sufficient to Maintain Pluripotency while Maintaining the expression of Oct3/4. Notably, overexpression of Nanog supports LIF-independent self-renewal of mouse ES cells in the absence of Klf4 and Tbx3 activity. Therefore, Klf4 and Tbx3 are involved in mediating LIF signalling to the core circuitry but are not directly associated with the maintenance of Pluripotency, because ES cells keep Pluripotency without their expression in the particular context.
Hans R. Schöler - One of the best experts on this subject based on the ideXlab platform.
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establishment of feeder free culture system for human induced pluripotent stem cell on das nanocrystalline graphene
Scientific Reports, 2016Co-Authors: Jaekyung Choi, Marcos J Arauzobravo, Soonyong Kwon, Holm Zaehres, Chan Young Park, Hyunwook Kang, Hans R. SchölerAbstract:The maintenance of undifferentiated human pluripotent stem cells (hPSC) under xeno-free condition requires the use of human feeder cells or extracellular matrix (ECM) coating. However, human-derived sources may cause human pathogen contamination by viral or non-viral agents to the patients. Here we demonstrate feeder-free and xeno-free culture system for hPSC expansion using diffusion assisted synthesis-grown nanocrystalline graphene (DAS-NG), a synthetic non-biological nanomaterial which completely rule out the concern of human pathogen contamination. DAS-NG exhibited advanced biocompatibilities including surface nanoroughness, oxygen containing functional groups and hydrophilicity. hPSC cultured on DAS-NG could Maintain Pluripotency in vitro and in vivo, and especially cell adhesion-related gene expression profile was comparable to those of cultured on feeders, while hPSC cultured without DAS-NG differentiated spontaneously with high expression of somatic cell-enriched adhesion genes. This feeder-free and xeno-free culture method using DAS-NG will facilitate the generation of clinical-grade hPSC.
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BRG1 Is Required to Maintain Pluripotency of Murine Embryonic Stem Cells
BioResearch open access, 2014Co-Authors: Nishant Singhal, Daniel Esch, Martin Stehling, Hans R. SchölerAbstract:BAF chromatin remodeling complexes containing the BRG1 protein have been shown to be not only essential for early embryonic development, but also paramount in enhancing the efficiency of reprogramming somatic cells to Pluripotency mediated by four transcription factors. To investigate the role of BRG1 in regulating Pluripotency, we found that Oct4 and Nanog levels were increased immediately after BRG1 knockdown. While Nanog levels remained elevated over the investigated time period, Oct4 levels decreased at later time points. Additionally, OCT4 target genes were also found to be upregulated upon Brg1 knockdown. SiRNA-mediated BRG1 knockdown in embryonic stem (ES) cells led to Oct4 and Nanog upregulation, whereas F9 cells showed primarily Oct4 upregulation. BRG1 knockdown upregulated the expression of differentiation markers in mouse ES cells as well as differentiated morphology under reduced leukemia inhibitory factor conditions. Our results show that BRG1 plays an important role in Maintaining Pluripotency by fine-tuning the expression level of Oct4 and other Pluripotency-associated genes.
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Neural Stem Cells Achieve and Maintain Pluripotency without Feeder Cells
PLOS ONE, 2011Co-Authors: Hyun Woo Choi, Sol Choi, Hyo Jin Jang, Youngsok Choi, Hans R. Schöler, Hyung Min ChungAbstract:Background: Differentiated cells can be reprogrammed into Pluripotency by transduction of four defined transcription factors. Induced pluripotent stem cells (iPS cells) are expected to be useful for regenerative medicine as well as basic research. Recently, the report showed that mouse embryonic fibroblasts (MEF) cells are not essential for reprogramming. However, in using fibroblasts as donor cells for reprogramming, individual fibroblasts that had failed to reprogram could function as feeder cells. Methodology/Principal Finding: Here, we show that adult mouse neural stem cells (NSCs), which are not functional feeder cells, can be reprogrammed into iPS cells using defined four factors (Oct4, Sox2, Klf4, and c-Myc) under feeder-free conditions. The iPS cells, generated from NSCs expressing the Oct4-GFP reporter gene, could proliferate for more than two months (passage 20). Generated and Maintained without feeder cells, these iPS cells expressed Pluripotency markers (Oct4 and Nanog), the promoter regions of Oct4 and Nanog were hypomethylated, could differentiated into to all three germ layers in vitro, and formed a germline chimera. These data indicate that NSCs can achieve and Maintain Pluripotency under feeder-free conditions. Conclusion/Significance: This study suggested that factors secreted by feeder cells are not essential in the initial/early stages of reprogramming and for Pluripotency maintenance. This technology might be useful for a human system, as a feeder-free reprogramming system may help generate iPS cells of a clinical grade for tissue or organ regeneration.
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Neural stem cells achieve and Maintain Pluripotency without feeder cells.
PloS one, 2011Co-Authors: Hyun Woo Choi, Sol Choi, Hyo Jin Jang, Youngsok Choi, Hans R. Schöler, Hyung Min Chung, Jong Soo Kim, Min Jung Kim, Jeong TaeAbstract:Background: Differentiated cells can be reprogrammed into Pluripotency by transduction of four defined transcription factors. Induced pluripotent stem cells (iPS cells) are expected to be useful for regenerative medicine as well as basic research. Recently, the report showed that mouse embryonic fibroblasts (MEF) cells are not essential for reprogramming. However, in using fibroblasts as donor cells for reprogramming, individual fibroblasts that had failed to reprogram could function as feeder cells. Methodology/Principal Finding: Here, we show that adult mouse neural stem cells (NSCs), which are not functional feeder cells, can be reprogrammed into iPS cells using defined four factors (Oct4, Sox2, Klf4, and c-Myc) under feeder-free conditions. The iPS cells, generated from NSCs expressing the Oct4-GFP reporter gene, could proliferate for more than two months (passage 20). Generated and Maintained without feeder cells, these iPS cells expressed Pluripotency markers (Oct4 and Nanog), the promoter regions of Oct4 and Nanog were hypomethylated, could differentiated into to all three germ layers in vitro, and formed a germline chimera. These data indicate that NSCs can achieve and Maintain Pluripotency under feeder-free conditions. Conclusion/Significance: This study suggested that factors secreted by feeder cells are not essential in the initial/early stages of reprogramming and for Pluripotency maintenance. This technology might be useful for a human system, as a feeder-free reprogramming system may help generate iPS cells of a clinical grade for tissue or organ regeneration.
