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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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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. |
format | Online Article Text |
id | pubmed-3422229 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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