Language

English

Publication Date

2-12-2025

Journal

Stem Cells

DOI

10.1093/stmcls/sxae080

PMID

40037390

PMCID

PMC11879289

PubMedCentral® Posted Date

3-3-2025

PubMedCentral® Full Text Version

Post-print

Abstract

The miR-290 and miR-302 clusters of microRNAs are highly expressed in naïve and primed pluripotent stem cells, respectively. Ectopic expression of the embryonic stem cell (ESC)-specific cell cycle regulating family of microRNAs arising from these two clusters dramatically enhances the reprogramming of both mouse and human somatic cells to induced pluripotency. Here, we used genetic knockouts to dissect the requirement for the miR-290 and miR-302 clusters during the reprogramming of mouse fibroblasts into induced pluripotent stem cells (iPSCs) with retrovirally introduced Oct4, Sox2, and Klf4. Knockout of either cluster alone did not negatively impact the efficiency of reprogramming. Resulting cells appeared identical to their ESC microRNA cluster knockout counterparts. In contrast, the combined loss of both clusters blocked the formation of iPSCs. While rare double knockout clones could be isolated, they showed a dramatically reduced proliferation rate, a persistent inability to fully silence the exogenously introduced pluripotency factors, and a transcriptome distinct from individual miR-290 or miR-302 mutant ESC and iPSCs. Taken together, our data show that miR-290 and miR-302 are essential yet interchangeable in reprogramming to the induced pluripotent state.

Keywords

MicroRNAs, Induced Pluripotent Stem Cells, Animals, Kruppel-Like Factor 4, Fibroblasts, Cellular Reprogramming, Mice, Humans, Cell Differentiation, stem cells, microRNAs, cellular reprogramming, induced pluripotent stem cells

Published Open-Access

yes

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