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Keywords:

  • miRNA;
  • Embryonic Stem Cells;
  • miR-290–295;
  • Pax6;
  • Differentiation;
  • Ectoderm;
  • Mesndoderm

Abstract

microRNAs of the miR-290–295 family are selectively expressed at high levels in mouse embryonic stem cells (mESCs) and have established roles in regulating self-renewal. However, the potential influence of these microRNAs on cell fate acquisition during differentiation has been overlooked. Here, we show that miR-290–295 regulate the propensity of mESCs to acquire specific fates. We generated a new miR-290–295-null mESC model, which exhibits increased propensity to generate ectoderm, at the expense of endoderm and mesoderm lineages. We further found that in wild-type cells, miR-290–295 repress Pax6 and ectoderm differentiation; accordingly, Pax6 knockdown partially rescues the mESCs differentiation impairment that is caused by loss of miR-290–295. Thus, in addition to regulating self-renewal, the large reservoir of miR-290–295 in undifferentiated mESCs fine-tunes the expression of master transcriptional factors, such as Pax6, thereby regulating the equilibrium of fate acquisition by mESC descendants. Stem Cells 2013;31:2266–2272