miR-142-3p regulates the formation and differentiation of hematopoietic stem cells in vertebrates

Cell Res. 2013 Dec;23(12):1356-68. doi: 10.1038/cr.2013.145. Epub 2013 Oct 29.

Abstract

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-142a-3p 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Cell Differentiation*
  • Core Binding Factor Alpha 2 Subunit / antagonists & inhibitors
  • Core Binding Factor Alpha 2 Subunit / genetics
  • Core Binding Factor Alpha 2 Subunit / metabolism
  • Embryo, Mammalian / metabolism
  • Embryo, Nonmammalian / metabolism
  • Gene Expression Regulation, Developmental*
  • HEK293 Cells
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / metabolism*
  • Humans
  • Interferon Regulatory Factor-7 / antagonists & inhibitors
  • Interferon Regulatory Factor-7 / genetics
  • Interferon Regulatory Factor-7 / metabolism
  • Mice
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Nitric Oxide / metabolism
  • Oligonucleotides, Antisense / metabolism
  • RNA Interference
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Zebrafish / genetics
  • Zebrafish / growth & development
  • Zebrafish / metabolism

Substances

  • 3' Untranslated Regions
  • Core Binding Factor Alpha 2 Subunit
  • Interferon Regulatory Factor-7
  • MIRN142 microRNA, zebrafish
  • MicroRNAs
  • Oligonucleotides, Antisense
  • Nitric Oxide