Brief report: miR-290–295 regulate embryonic stem cell differentiation propensities by repressing pax6

Authors


  • Author contributions : H.K., E.C., M.L., E.H., and Y.S.: designed the research; H.K.: performed all the work reported in this manuscript, except for establishment of the miR-290–295 null ESC line (E.C., M.L, and G.B.); H.K., E.H., and Y.S.: wrote the manuscript with comments from E.C. H.K. and E.C. contributed equally to this article.

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

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