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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

Authors

  • Galan-Caridad JM
  • Harel S
  • Arenzana TL
  • Hou ZE
  • Doetsch FK
  • Mirny LA
  • Reizis B

Journal

Cell

Publication Data

April 20, 2007

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI007525
  • Agency: NIAID NIH HHS, Id: AI066459
  • Agency: NIAID NIH HHS, Id: F31 AI066459-02
  • Agency: NHLBI NIH HHS, Id: HL084353
  • Agency: NIAID NIH HHS, Id: R01 AI072571
  • Agency: NHLBI NIH HHS, Id: R01 HL084353
  • Agency: NHLBI NIH HHS, Id: R01 HL084353-01
  • Agency: NIAID NIH HHS, Id: R21 AI085439
  • Agency: NIAID NIH HHS, Id: T32 AI007525
  • Agency: NIAID NIH HHS, Id: T32 AI007525-10

Mesh Terms

  • 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