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

作者：Ryan M. O’Connell, Aadel A. Chaudhuri, Dinesh S. Rao, William S. Gibson, Alejandro B. Balazs, David Baltimore · 发表于：Proceedings of the National Academy of Sciences · 年份：2010 · DOI：10.1073/pnas.1009798107 · 被引用次数：282 · 研究领域：MicroRNA in disease regulation、Extracellular vesicles in disease、Hematopoietic Stem Cell Transplantation

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.