ZFX controls the self-renewal of human embryonic stem cells Journal Article
| Authors: | Harel, S.; Tu, E. Y.; Weisberg, S.; Esquilin, M.; Chambers, S. M.; Liu, B.; Carson, C. T.; Studer, L.; Reizis, B.; Tomishima, M. J. |
| Article Title: | ZFX controls the self-renewal of human embryonic stem cells |
| Abstract: | Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) offer great promise in regenerative medicine and disease modeling due to their unlimited self-renewal and broad differentiation capacity. There is evidence that the growth properties and critical signaling pathways differ between murine and human ESCs; therefore, it is essential to perform functional studies to test the putatively conserved mechanisms of pluripotent stem cell self-renewal between species. Previously, we identified the transcription factor Zfx as a key regulator of self-renewal in murine ESCs. Here we extend those findings to human ESCs. ZFX knockdown in hESCs hindered clonal growth and decreased colony size after serial replating. ZFX overexpression enhanced clone formation in the presence of Y-27632, increased colony size at low density and decreased expression of differentiation-related genes in human ESCs. ZFX-overexpressing hESCs resisted spontaneous differentiation but could be directed to differentiate into endodermal and neural cell fates when provided with the appropriate cues. Thus, ZFX acts as a molecular rheostat regulating the balance between self-renewal and differentiation in hESCs, revealing the close evolutionary conservation of the self-renewal mechanisms in murine and human ESCs. © 2012 Harel et al. |
| Keywords: | controlled study; protein expression; unclassified drug; human cell; protein function; cell proliferation; animals; mice; gene expression profiling; cell growth; embryonic stem cell; cell line; transcription factor; cell fate; cell renewal; cell differentiation; chromosomes, artificial, bacterial; gene expression regulation; regulatory mechanism; kruppel-like transcription factors; embryonic stem cells; cell size; cell density; pluripotent stem cell; gene silencing; cell clone; nerve cell; clone cells; gene knockdown techniques; transgenes; endoderm; clonogenesis; 4 (1 aminoethyl) n (4 pyridyl)cyclohexanecarboxamide; cellular parameters; transcription factor zfx; colony size |
| Journal Title: | PLoS ONE |
| Volume: | 7 |
| Issue: | 8 |
| ISSN: | 1932-6203 |
| Publisher: | Public Library of Science |
| Date Published: | 2012-01-01 |
| Start Page: | e42302 |
| Language: | English |
| DOI: | 10.1371/journal.pone.0042302 |
| PROVIDER: | scopus |
| PMCID: | PMC3411758 |
| PUBMED: | 22879936 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 4 September 2012" - "Source: Scopus" |
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