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

Cell. 2007 Apr 20;129(2):345-57. doi: 10.1016/j.cell.2007.03.014.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Differentiation
  • Cell Proliferation
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / metabolism
  • Female
  • Gene Expression
  • Gene Targeting
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / metabolism
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism*
  • Male
  • Mice
  • Proto-Oncogene Proteins / genetics
  • T-Box Domain Proteins / genetics

Substances

  • Kruppel-Like Transcription Factors
  • Proto-Oncogene Proteins
  • T-Box Domain Proteins
  • Tbx3 protein, mouse
  • Tcl1 protein, mouse
  • zinc finger protein, X-linked

Associated data

  • GEO/GSE7069