MicroRNA-based Discovery of Barriers to Dedifferentiation of Fibroblasts to Pluripotent Stem Cells

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2013 Sep 17

PMID 24037508

Citations 33

Authors

Robert L Judson

Tobias S Greve

Ronald J Parchem

Robert Blelloch

Affiliations

Soon will be listed here.

Abstract

Individual microRNAs (miRNAs) can target hundreds of mRNAs forming networks of presumably cooperating genes. To test this presumption, we functionally screened miRNAs and their targets in the context of dedifferentiation of mouse fibroblasts to induced pluripotent stem cells (iPSCs). Along with the miR-302-miR-294 family, the miR-181 family arose as a previously unidentified enhancer of the initiation phase of reprogramming. Endogenous miR-181 miRNAs were transiently elevated with the introduction of Pou5f1 (also known as Oct4), Sox2 and Klf4 (referred to as OSK), and miR-181 inhibition diminished iPSC colony formation. We tested the functional contribution of 114 individual targets of the two families, revealing 25 genes that normally suppress initiation. Coinhibition of targets cooperatively promoted both the frequency and kinetics of OSK-induced reprogramming. These data establish two of the largest functionally defined networks of miRNA-mRNA interactions and reveal previously unidentified relationships among genes that act together to suppress early stages of reprogramming.

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 Multifaceted Roles of MicroRNA-181 in Stem Cell Differentiation and Cancer Stem Cell Plasticity.

Yang C, Wang R, Hardy P Cells. 2025; 14(2.

PMID: 39851559 PMC: 11763446. DOI: 10.3390/cells14020132.

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.

Combinatorial targeting of a specific EMT/MET network by macroH2A variants safeguards mesenchymal identity.

Valakos D, Klagkou E, Kokkalis A, Polyzos A, Kyrilis F, Banos A PLoS One. 2023; 18(7):e0288005.

PMID: 37432970 PMC: 10335705. DOI: 10.1371/journal.pone.0288005.

MicroRNA Roles in Cell Reprogramming Mechanisms.

Pascale E, Caiazza C, Paladino M, Parisi S, Passaro F, Caiazzo M Cells. 2022; 11(6).

PMID: 35326391 PMC: 8946776. DOI: 10.3390/cells11060940.

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