Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Cell. 2012 Mar 2;148(5):1001-14. doi: 10.1016/j.cell.2012.01.040.

A differentiation checkpoint limits hematopoietic stem cell self-renewal in response to DNA damage.

Author information

  • 1Institute of Molecular Medicine and Max-Planck-Research Department of Stem Cell Aging, University of Ulm, Ulm, Germany.

Abstract

Checkpoints that limit stem cell self-renewal in response to DNA damage can contribute to cancer protection but may also promote tissue aging. Molecular components that control stem cell responses to DNA damage remain to be delineated. Using in vivo RNAi screens, we identified basic leucine zipper transcription factor, ATF-like (BATF) as a major component limiting self-renewal of hematopoietic stem cells (HSCs) in response to telomere dysfunction and γ-irradiation. DNA damage induces BATF in a G-CSF/STAT3-dependent manner resulting in lymphoid differentiation of HSCs. BATF deletion improves HSC self-renewal and function in response to γ-irradiation or telomere shortening but results in accumulation of DNA damage in HSCs. Analysis of bone marrow from patients with myelodysplastic syndrome supports the conclusion that DNA damage-dependent induction of BATF is conserved in human HSCs. Together, these results provide experimental evidence that a BATF-dependent differentiation checkpoint limits self-renewal of HSCs in response to DNA damage.

Copyright © 2012 Elsevier Inc. All rights reserved.

Comment in

PMID:
22385964
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk