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MicroRNA miR-125a controls hematopoietic stem cell number
Abstract
MicroRNAs influence hematopoietic differentiation, but little is known about their effects on the stem cell state. Here, we report that the microRNA processing enzyme Dicer is essential for stem cell persistence in vivo and a specific microRNA, miR-125a, controls the size of the stem cell population by regulating hematopoietic stem/progenitor cell (HSPC) apoptosis. Conditional deletion of Dicer revealed an absolute dependence for the multipotent HSPC population in a cell-autonomous manner, with increased HSPC apoptosis in mutant animals. An evolutionarily conserved microRNA cluster containing miR-99b, let-7e, and miR-125a was preferentially expressed in long-term hematopoietic stem cells. MicroRNA miR-125a alone was capable of increasing the number of hematopoietic stem cells in vivo by more than 8-fold. This result was accomplished through a differentiation stage-specific reduction of apoptosis in immature hematopoietic progenitors, possibly through targeting multiple proapoptotic genes. Bak1 was directly down-regulated by miR-125a and expression of a 3′UTR-less Bak1 blocked miR-125a-induced hematopoietic expansion in vivo. These data demonstrate cell-state-specific regulation by microRNA and identify a unique microRNA functioning to regulate the stem cell pool size.
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Impairing mature miR expression by KO of processing machinery in Dicer-KO experiments revealed miR dependency for HSCs and osteoclast development.
“At a more global level, impairing mature miR expression by KO of the processing machinery in Dicer-KO experiments revealed miR dependency for HSCs 14 and osteoclast development.15”
From Macrophage development from HSCs requires PU.1-coordinated microRNA expression (2011) · cites this paper as [14]
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Metadata
- Authors
- Guo, S., Lu, J., Schlanger, R., Zhang, H., Wang, J. Y., Fox, M. C., Purton, L. E., Fleming, H. H., Cobb, B., Merkenschlager, M., Golub, T. R., & Scadden, D. T.
- Affiliations
- Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;
- Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142;
- Lymphocyte Development Group, Medical Research Center Clinical Sciences Centre, Imperial College London, London W12 0NN, United Kingdom; and
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-07-08
- Volume
- 107
- Issue
- 32
- Pages
- 14229-14234
- ISSN
- 0027-8424
- 1091-6490
- Cited by
- 310
- References
- 6
- Language
- en
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