Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Cell. 2006 Aug 25;126(4):755-66.

Multilineage transcriptional priming and determination of alternate hematopoietic cell fates.

Author information

  • 1Howard Hughes Medical Institute and Department of Molecular Genetics and Cell Biology, The University of Chicago, 929 East 57th Street, GCIS W522, IL 60637, USA.

Abstract

Hematopoietic stem cells and their progenitors exhibit multilineage patterns of gene expression. Molecular mechanisms underlying the generation and refinement of these patterns during cell fate determination remain unexplored because of the absence of suitable experimental systems. Using PU.1(-/-) progenitors, we demonstrate that at subthreshold levels, this Ets transcription factor regulates a mixed pattern (macrophage/neutrophil) of gene expression within individual myeloid progenitors. Increased PU.1 levels refine the pattern and promote macrophage differentiation by modulating a novel regulatory circuit comprised of counter antagonistic repressors, Egr-1,2/Nab-2 and Gfi-1. Egr-1 and Egr-2 function redundantly to activate macrophage genes and to repress the neutrophil program. These results are used to assemble and mathematically model a gene regulatory network that exhibits both graded and bistable behaviors and accounts for the onset and resolution of mixed lineage patterns during cell fate determination.

Comment in

PMID:
16923394
[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 Icon for Faculty of 1000
    Loading ...
    Write to the Help Desk