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Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14235-40. doi: 10.1073/pnas.1009798107. Epub 2010 Jul 26.

MicroRNAs enriched in hematopoietic stem cells differentially regulate long-term hematopoietic output.

Author information

1
Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.

Abstract

The production of blood cells depends on a rare hematopoietic stem-cell (HSC) population, but the molecular mechanisms underlying HSC biology remain incompletely understood. Here, we identify a subset of microRNAs (miRNAs) that is enriched in HSCs compared with other bone-marrow cells. An in vivo gain-of-function screen found that three of these miRNAs conferred a competitive advantage to engrafting hematopoietic cells, whereas other HSC miRNAs attenuated production of blood cells. Overexpression of the most advantageous miRNA, miR-125b, caused a dose-dependent myeloproliferative disorder that progressed to a lethal myeloid leukemia in mice and also enhanced hematopoietic engraftment in human immune system mice. Our study identifies an evolutionarily conserved subset of miRNAs that is expressed in HSCs and functions to modulate hematopoietic output.

PMID:
20660734
PMCID:
PMC2922591
DOI:
10.1073/pnas.1009798107
[Indexed for MEDLINE]
Free PMC Article

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