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.
authors.affiliation: Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Sivan
authors.initials: S
authors.lastname: Harel
authors.forename: Edmund Y
authors.initials: EY
authors.lastname: Tu
authors.forename: Stuart
authors.initials: S
authors.lastname: Weisberg
authors.forename: Manuel
authors.initials: M
authors.lastname: Esquilin
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Chambers
authors.forename: Becky
authors.initials: B
authors.lastname: Liu
authors.forename: Christian T
authors.initials: CT
authors.lastname: Carson
authors.forename: Lorenz
authors.initials: L
authors.lastname: Studer
authors.forename: Boris
authors.initials: B
authors.lastname: Reizis
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Tomishima
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation; D048429:Cell Size; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D002999:Clone Cells; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D004707:Endoderm / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D019076:Transgenes / Q000235:genetics
chemical_list: D051741:Kruppel-Like Transcription Factors; C062076:zinc finger protein, X-linked