Journal
CELL RESEARCH
Volume 23, Issue 12, Pages 1356-1368Publisher
INST BIOCHEMISTRY & CELL BIOLOGY
DOI: 10.1038/cr.2013.145
Keywords
hematopoietic stem cell; miR-142a-3p; irf7; zebrafish; mouse
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Funding
- National Basic Research Program of China [2010CB945300, 2011CB943900, 2012CB945101]
- National Natural Science Foundation of China [31271570, 90919055]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA01010110]
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Previous studies on developmental hematopoiesis have mainly focused on signaling and transcription factors, while the appreciation of epigenetic regulation including that of microRNAs is recent. Here, we show that in zebrafish and mouse, miR-142-3p is specifically expressed in hematopoietic stem cells (HSCs). Knockdown of miR-142a3p in zebrafish led to a reduced population of HSCs in the aorta-gonad-mesonephros (AGM) region as well as T-cell defects in the thymus. Mechanistically, miR-142a-3p regulates HSC formation and differentiation through the repression of interferon regulatory factor 7 (irf7)-mediated inflammation signaling. Finally, we show that miR-142-3p is also involved in the development of HSCs in mouse AGM, suggesting that it has a highly conserved role in vertebrates. Together, these findings unveil the pivotal roles that miR-142a-3p plays in the formation and differentiation of HSCs by repressing irf7 signaling.
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