Opposing microRNA families regulate self-renewal in mouse embryonic stem cells

Article

关键词: TRANSCRIPTIONAL NETWORK;    DNA METHYLATION;    C-MYC;    PLURIPOTENCY;    RNA;    DIFFERENTIATION;    EXPRESSION;    LIN-28;    NANOG;    URIDYLATION;   

DOI  :  10.1038/nature08725

来源: SCIE

【 摘 要 】

When embryonic stem cells (ESCs) differentiate, they must both silence the ESC self-renewal program and activate new tissue-specific programs. In the absence of DGCR8 (Dgcr8(-/-)), a protein required for microRNA (miRNA) biogenesis, mouse ESCs are unable to silence self-renewal. Here we show that the introduction of let-7 miRNAs-a family of miRNAs highly expressed in somatic cells-can suppress self-renewal in Dgcr8(-/-) but not wild-type ESCs. Introduction of ESC cell cycle regulating (ESCC) miRNAs into the Dgcr8(-/-) ESCs blocks the capacity of let-7 to suppress self-renewal. Profiling and bioinformatic analyses show that let-7 inhibits whereas ESCC miRNAs indirectly activate numerous self-renewal genes. Furthermore, inhibition of the let-7 family promotes de-differentiation of somatic cells to induced pluripotent stem cells. Together, these findings show how the ESCC and let-7 miRNAs act through common pathways to alternatively stabilize the self-renewing versus differentiated cell fates.

【 授权许可】

Free