Zfx controls self-renewal of human embryonic stem cells

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, increased colony size 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. Human embryonic stem cells with over expression of ZFX were compared to the original cell line (H9) and a clonally derived wild-type cell line (clone 3)