Zfx controls the self-renewal of embryonic and hematopoietic stem cells

Stem cells (SC) exhibit a unique capacity for self-renewal in an undifferentiated state. It is unclear whether the self-renewal of pluripotent embryonic SC (ESC) and of tissue-specific adult SC such as hernatopoietic SC (HSC) is controlled by common mechanisms. The deletion of transcription factor Zfx impaired the selfrenewal but not the differentiation capacity of murine ESC; conversely, Zfx overexpression facilitated ESC self-renewal by opposing differentiation. Furthermore, Zfx deletion abolished the maintenance of adult HSC but did not affect erythromyeloid progenitors or fetal HSC. Zfxdeficient ESC and HSC showed increased apoptosis and SC-specific upregulation of stressinducible genes. Zfx directly activated common target genes in ESC and HSC, as well as ESCspecific target genes including ESC selfrenewal regulators Tbx3 and Tcl1. These studies identify Zfx as a shared transcriptional regulator of ESC and HSC, suggesting a common genetic basis of self-renewal in embryonic and adult SC.