Opposing MicroRNA Families Regulate Self-renewal in Mouse Embryonic Stem Cells

Overview

Journal Nature

Specialty Science

Date 2010 Jan 8

PMID 20054295

Citations 377

Authors

Collin Melton

Robert L Judson

Robert Blelloch

Affiliations

Soon will be listed here.

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.

Citing Articles

The miR-290 and miR-302 clusters are essential for reprogramming of fibroblasts to induced pluripotent stem cells.

Ye J, Boileau R, Parchem R, Judson-Torres R, Blelloch R Stem Cells. 2025; 43(2).

PMID: 40037390 PMC: 11879289. DOI: 10.1093/stmcls/sxae080.

The miR-290 and miR-302 clusters are essential for reprogramming of fibroblasts to induced pluripotent stem cells.

Ye J, Boileau R, Parchem R, Judson-Torres R, Blelloch R bioRxiv. 2024; .

PMID: 39282363 PMC: 11398367. DOI: 10.1101/2024.09.02.610895.

The role of Lin28A and Lin28B in cancer beyond Let-7.

Cotino-Najera S, Garcia-Villa E, Cruz-Rosales S, Gariglio P, Diaz-Chavez J FEBS Lett. 2024; 598(24):2963-2979.

PMID: 39152528 PMC: 11665955. DOI: 10.1002/1873-3468.15004.

Elucidation of how the Mir-23-27-24 cluster regulates development and aging.

Yap X, Chen J Exp Mol Med. 2024; 56(6):1263-1271.

PMID: 38871817 PMC: 11263685. DOI: 10.1038/s12276-024-01266-3.

MiR-290 Family Maintains Pluripotency and Self-Renewal by Regulating MAPK Signaling Pathway in Intermediate Pluripotent Stem Cells.

Liu Y, Li X, Ma X, Du Q, Wang J, Yu H Int J Mol Sci. 2024; 25(5).

PMID: 38473927 PMC: 10931995. DOI: 10.3390/ijms25052681.

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