Zfx Controls the Self-Renewal of Embryonic and Hematopoietic Stem Cells

Autor: Teresita L. Arenzana, Jose M. Galan-Caridad, Leonid A. Mirny, Z. Esther Hou, Sivan Harel, Fiona Doetsch, Boris Reizis
Rok vydání: 2007
Předmět:
Zdroj: Cell. 129:345-357
ISSN: 0092-8674
DOI: 10.1016/j.cell.2007.03.014
Popis: SummaryStem 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.
Databáze: OpenAIRE