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• W1971645224 abstract "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. Differentiation of an embryonic stem cell (ESC) requires both suppression of self-renewal and activation of a specific differentiation pathway. The small non-coding RNAs known as microRNAs (miRNAs) are emerging as important players in the orchestration of cell fate. Now the prominent miRNA, let-7, is shown to be responsible for suppressing the self-renewal program in ESCs. This inhibition can be reversed by a family of ESC-regulating (ESCC) miRNAs that regulate the cell cycle, suggesting that the interplay between let-7 and ESCC miRNAs provides a mechanism capable of dictating cell fate. The differentiation of an embryonic stem cell (ESC) requires both suppression of the self-renewal process and activation of the specific differentiation pathway. The let-7 family of microRNAs (miRNAs) are now shown to suppress the self-renewal program in cells that are normally unable to silence this program, whereas introduction of ESC cell cycle regulating miRNAs blocks the action of let-7. Thus, the interplay between these two groups of miRNAs dictates cell fate." @default.
• W1971645224 created "2016-06-24" @default.
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• W1971645224 creator A5083816703 @default.
• W1971645224 creator A5084599285 @default.
• W1971645224 date "2010-01-06" @default.
• W1971645224 modified "2023-10-12" @default.
• W1971645224 title "Opposing microRNA families regulate self-renewal in mouse embryonic stem cells" @default.
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• W1971645224 doi "https://doi.org/10.1038/nature08725" @default.
• W1971645224 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2894702" @default.
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