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 hematopoietic SC (HSC) is controlled by common mechanisms. The deletion of transcription factor Zfx impaired the self-renewal 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. Zfx-deficient ESC and HSC showed increased apoptosis and SC-specific upregulation of stress-inducible genes. Zfx directly activated common target genes in ESC and HSC, as well as ESC-specific target genes including ESC self-renewal 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.
Pubmed ID: 17448993 RIS Download
Animals | Apoptosis | Cell Differentiation | Cell Proliferation | Embryonic Stem Cells | Female | Gene Expression | Gene Targeting | Hematopoietic Stem Cells | Kruppel-Like Transcription Factors | Male | Mice | Proto-Oncogene Proteins | T-Box Domain Proteins