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MiR-25 Regulates Wwp2 and Fbxw7 and Promotes Reprogramming of Mouse Fibroblast Cells to iPSCs

BACKGROUND: miRNAs are a class of small non-coding RNAs that regulate gene expression and have critical functions in various biological processes. Hundreds of miRNAs have been identified in mammalian genomes but only a small number of them have been functionally characterized. Recent studies also de...

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Autores principales: Lu, Dong, Davis, Matthew P. A., Abreu-Goodger, Cei, Wang, Wei, Campos, Lia S., Siede, Julia, Vigorito, Elena, Skarnes, William C., Dunham, Ian, Enright, Anton J., Liu, Pentao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422229/
https://www.ncbi.nlm.nih.gov/pubmed/22912667
http://dx.doi.org/10.1371/journal.pone.0040938
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author Lu, Dong
Davis, Matthew P. A.
Abreu-Goodger, Cei
Wang, Wei
Campos, Lia S.
Siede, Julia
Vigorito, Elena
Skarnes, William C.
Dunham, Ian
Enright, Anton J.
Liu, Pentao
author_facet Lu, Dong
Davis, Matthew P. A.
Abreu-Goodger, Cei
Wang, Wei
Campos, Lia S.
Siede, Julia
Vigorito, Elena
Skarnes, William C.
Dunham, Ian
Enright, Anton J.
Liu, Pentao
author_sort Lu, Dong
collection PubMed
description BACKGROUND: miRNAs are a class of small non-coding RNAs that regulate gene expression and have critical functions in various biological processes. Hundreds of miRNAs have been identified in mammalian genomes but only a small number of them have been functionally characterized. Recent studies also demonstrate that some miRNAs have important roles in reprogramming somatic cells to induced pluripotent stem cells (iPSCs). METHODS: We screened 52 miRNAs cloned in a piggybac (PB) vector for their roles in reprogramming of mouse embryonic fibroblast cells to iPSCs. To identify targets of miRNAs, we made Dgcr8-deficient embryonic stem (ES) cells and introduced miRNA mimics to these cells, which lack miRNA biogenesis. The direct target genes of miRNA were identified through global gene expression analysis and target validation. RESULTS AND CONCLUSION: We found that over-expressing miR-25 or introducing miR-25 mimics enhanced production of iPSCs. We identified a number of miR-25 candidate gene targets. Of particular interest were two ubiquitin ligases, Wwp2 and Fbxw7, which have been proposed to regulate Oct4, c-Myc and Klf5, respectively. Our findings thus highlight the complex interplay between miRNAs and transcription factors involved in reprogramming, stem cell self-renewal and maintenance of pluripotency.
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spelling pubmed-34222292012-08-21 MiR-25 Regulates Wwp2 and Fbxw7 and Promotes Reprogramming of Mouse Fibroblast Cells to iPSCs Lu, Dong Davis, Matthew P. A. Abreu-Goodger, Cei Wang, Wei Campos, Lia S. Siede, Julia Vigorito, Elena Skarnes, William C. Dunham, Ian Enright, Anton J. Liu, Pentao PLoS One Research Article BACKGROUND: miRNAs are a class of small non-coding RNAs that regulate gene expression and have critical functions in various biological processes. Hundreds of miRNAs have been identified in mammalian genomes but only a small number of them have been functionally characterized. Recent studies also demonstrate that some miRNAs have important roles in reprogramming somatic cells to induced pluripotent stem cells (iPSCs). METHODS: We screened 52 miRNAs cloned in a piggybac (PB) vector for their roles in reprogramming of mouse embryonic fibroblast cells to iPSCs. To identify targets of miRNAs, we made Dgcr8-deficient embryonic stem (ES) cells and introduced miRNA mimics to these cells, which lack miRNA biogenesis. The direct target genes of miRNA were identified through global gene expression analysis and target validation. RESULTS AND CONCLUSION: We found that over-expressing miR-25 or introducing miR-25 mimics enhanced production of iPSCs. We identified a number of miR-25 candidate gene targets. Of particular interest were two ubiquitin ligases, Wwp2 and Fbxw7, which have been proposed to regulate Oct4, c-Myc and Klf5, respectively. Our findings thus highlight the complex interplay between miRNAs and transcription factors involved in reprogramming, stem cell self-renewal and maintenance of pluripotency. Public Library of Science 2012-08-17 /pmc/articles/PMC3422229/ /pubmed/22912667 http://dx.doi.org/10.1371/journal.pone.0040938 Text en © 2012 Lu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Lu, Dong
Davis, Matthew P. A.
Abreu-Goodger, Cei
Wang, Wei
Campos, Lia S.
Siede, Julia
Vigorito, Elena
Skarnes, William C.
Dunham, Ian
Enright, Anton J.
Liu, Pentao
MiR-25 Regulates Wwp2 and Fbxw7 and Promotes Reprogramming of Mouse Fibroblast Cells to iPSCs
title MiR-25 Regulates Wwp2 and Fbxw7 and Promotes Reprogramming of Mouse Fibroblast Cells to iPSCs
title_full MiR-25 Regulates Wwp2 and Fbxw7 and Promotes Reprogramming of Mouse Fibroblast Cells to iPSCs
title_fullStr MiR-25 Regulates Wwp2 and Fbxw7 and Promotes Reprogramming of Mouse Fibroblast Cells to iPSCs
title_full_unstemmed MiR-25 Regulates Wwp2 and Fbxw7 and Promotes Reprogramming of Mouse Fibroblast Cells to iPSCs
title_short MiR-25 Regulates Wwp2 and Fbxw7 and Promotes Reprogramming of Mouse Fibroblast Cells to iPSCs
title_sort mir-25 regulates wwp2 and fbxw7 and promotes reprogramming of mouse fibroblast cells to ipscs
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422229/
https://www.ncbi.nlm.nih.gov/pubmed/22912667
http://dx.doi.org/10.1371/journal.pone.0040938
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