Opposing microRNA families regulate self-renewal in mouse embryonic stem cells
作者： Collin Melton , Robert L. Judson , Robert Blelloch
DOI: 10.1038/NATURE08725
关键词: microRNA 、 Cell biology 、 Induced pluripotent stem cell 、 Embryonic stem cell 、 Biology 、 Stem cell 、 Cellular differentiation 、 Somatic cell 、 Gene silencing 、 DGCR8 、 Genetics
摘要: When embryonic stem cells (ESCs) differentiate, they must both silence the ESC self-renewal program and activate new tissue-specific programs. In absence of DGCR8 (Dgcr8(-/-)), a protein required for microRNA (miRNA) biogenesis, mouse ESCs are unable to self-renewal. Here we show that introduction let-7 miRNAs-a family miRNAs highly expressed in somatic cells-can suppress Dgcr8(-/-) but not wild-type ESCs. Introduction cell cycle regulating (ESCC) into blocks capacity Profiling bioinformatic analyses inhibits whereas ESCC indirectly numerous genes. Furthermore, inhibition promotes de-differentiation induced pluripotent cells. Together, these findings how act through common pathways alternatively stabilize self-renewing versus differentiated fates.
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