Format

Send to

Choose Destination
See comment in PubMed Commons below
Cell Stem Cell. 2007 Sep 13;1(3):324-37. doi: 10.1016/j.stem.2007.05.019.

Unique and independent roles for MLL in adult hematopoietic stem cells and progenitors.

Author information

  • 1Department of Genetics and Norris Cotton Cancer Center, Dartmouth Medical School, 725 Remsen, HB7400, Hanover, NH 03755, USA.

Abstract

The Mixed Lineage Leukemia (MLL) gene is essential for embryonic hematopoietic stem cell (HSC) development, but its role during adult hematopoiesis is unknown. Using an inducible knockout model, we demonstrate that Mll is essential for the maintenance of adult HSCs and progenitors, with fatal bone marrow failure occurring within 3 weeks of Mll deletion. Mll-deficient cells are selectively lost from mixed bone marrow chimeras, demonstrating their failure to self-renew even in an intact bone marrow environment. Surprisingly, HSCs lacking Mll exhibit ectopic cell-cycle entry, resulting in the depletion of quiescent HSCs. In contrast, Mll deletion in myelo-erythroid progenitors results in reduced proliferation and reduced response to cytokine-induced cell-cycle entry. Committed lymphoid and myeloid cells no longer require Mll, defining the early multipotent stages of hematopoiesis as Mll dependent. These studies demonstrate that Mll plays selective and independent roles within the hematopoietic system, maintaining quiescence in HSCs and promoting proliferation in progenitors.

PMID:
18371366
PMCID:
PMC2234224
DOI:
10.1016/j.stem.2007.05.019
[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center