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

Ryan M. O'Connell, Aadel A. Chaudhuri, Dinesh S. Rao, William S.J. Gibson, Alejandro B. Balazs, David Baltimore

Research output: Contribution to journalArticle

203 Scopus citations

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.

Original languageEnglish
Pages (from-to)14235-14240
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number32
DOIs
StatePublished - Aug 10 2010
Externally publishedYes

Keywords

  • Cancer
  • Inflammation
  • Myeloid
  • Noncoding RNA
  • Xenograft

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