Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 107, Issue 32, Pages 14235-14240Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1009798107
Keywords
cancer; inflammation; myeloid; xenograft; noncoding RNA
Categories
Funding
- Cancer Research Institute
- National Heart, Lung, and Blood Institute [K99HL102228]
- National Science Foundation
- National Cancer Institute [1K08CA133521]
- American Foundation for AIDS Research (amfAR) [107756-47-RFVA]
- National Institutes of Health [1R01AI079243-01]
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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.
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