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The miR-590/Acvr2a/Terf1 Axis Regulates Telomere Elongation and Pluripotency of Mouse iPSCs
During reprogramming, telomere re-elongation is important for pluripotency acquisition and ensures the high quality of induced pluripotent stem cells (iPSCs), but the regulatory mechanism remains largely unknown. Our study showed that fully reprogrammed mature iPSCs or mouse embryonic stem cells exp...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6066996/ https://www.ncbi.nlm.nih.gov/pubmed/29910124 http://dx.doi.org/10.1016/j.stemcr.2018.05.008 |
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author | Liu, Qidong Wang, Guiying Lyu, Yao Bai, Mingliang Jiapaer, Zeyidan Jia, Wenwen Han, Tong Weng, Rong Yang, Yiwei Yu, Yangyang Kang, Jiuhong |
author_facet | Liu, Qidong Wang, Guiying Lyu, Yao Bai, Mingliang Jiapaer, Zeyidan Jia, Wenwen Han, Tong Weng, Rong Yang, Yiwei Yu, Yangyang Kang, Jiuhong |
author_sort | Liu, Qidong |
collection | PubMed |
description | During reprogramming, telomere re-elongation is important for pluripotency acquisition and ensures the high quality of induced pluripotent stem cells (iPSCs), but the regulatory mechanism remains largely unknown. Our study showed that fully reprogrammed mature iPSCs or mouse embryonic stem cells expressed higher levels of miR-590-3p and miR-590-5p than pre-iPSCs. Ectopic expression of either miR-590-3p or miR-590-5p in pre-iPSCs improved telomere elongation and pluripotency. Activin receptor II A (Acvr2a) is the downstream target and mediates the function of miR-590. Downregulation of Acvr2a promoted telomere elongation and pluripotency. Overexpression of miR-590 or inhibition of ACTIVIN signaling increased telomeric repeat binding factor 1 (Terf1) expression. The p-SMAD2 showed increased binding to the Terf1 promoter in pre-iPSCs compared with mature iPSCs. Downregulation of Terf1 blocked miR-590- or shAcvr2a-mediated promotion of telomere elongation and pluripotency in pre-iPSCs. This study elucidated the role of the miR-590/Acvr2a/Terf1 signaling pathway in modulating telomere elongation and pluripotency in pre-iPSCs. |
format | Online Article Text |
id | pubmed-6066996 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-60669962018-08-01 The miR-590/Acvr2a/Terf1 Axis Regulates Telomere Elongation and Pluripotency of Mouse iPSCs Liu, Qidong Wang, Guiying Lyu, Yao Bai, Mingliang Jiapaer, Zeyidan Jia, Wenwen Han, Tong Weng, Rong Yang, Yiwei Yu, Yangyang Kang, Jiuhong Stem Cell Reports Article During reprogramming, telomere re-elongation is important for pluripotency acquisition and ensures the high quality of induced pluripotent stem cells (iPSCs), but the regulatory mechanism remains largely unknown. Our study showed that fully reprogrammed mature iPSCs or mouse embryonic stem cells expressed higher levels of miR-590-3p and miR-590-5p than pre-iPSCs. Ectopic expression of either miR-590-3p or miR-590-5p in pre-iPSCs improved telomere elongation and pluripotency. Activin receptor II A (Acvr2a) is the downstream target and mediates the function of miR-590. Downregulation of Acvr2a promoted telomere elongation and pluripotency. Overexpression of miR-590 or inhibition of ACTIVIN signaling increased telomeric repeat binding factor 1 (Terf1) expression. The p-SMAD2 showed increased binding to the Terf1 promoter in pre-iPSCs compared with mature iPSCs. Downregulation of Terf1 blocked miR-590- or shAcvr2a-mediated promotion of telomere elongation and pluripotency in pre-iPSCs. This study elucidated the role of the miR-590/Acvr2a/Terf1 signaling pathway in modulating telomere elongation and pluripotency in pre-iPSCs. Elsevier 2018-06-14 /pmc/articles/PMC6066996/ /pubmed/29910124 http://dx.doi.org/10.1016/j.stemcr.2018.05.008 Text en © 2018 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Liu, Qidong Wang, Guiying Lyu, Yao Bai, Mingliang Jiapaer, Zeyidan Jia, Wenwen Han, Tong Weng, Rong Yang, Yiwei Yu, Yangyang Kang, Jiuhong The miR-590/Acvr2a/Terf1 Axis Regulates Telomere Elongation and Pluripotency of Mouse iPSCs |
title | The miR-590/Acvr2a/Terf1 Axis Regulates Telomere Elongation and Pluripotency of Mouse iPSCs |
title_full | The miR-590/Acvr2a/Terf1 Axis Regulates Telomere Elongation and Pluripotency of Mouse iPSCs |
title_fullStr | The miR-590/Acvr2a/Terf1 Axis Regulates Telomere Elongation and Pluripotency of Mouse iPSCs |
title_full_unstemmed | The miR-590/Acvr2a/Terf1 Axis Regulates Telomere Elongation and Pluripotency of Mouse iPSCs |
title_short | The miR-590/Acvr2a/Terf1 Axis Regulates Telomere Elongation and Pluripotency of Mouse iPSCs |
title_sort | mir-590/acvr2a/terf1 axis regulates telomere elongation and pluripotency of mouse ipscs |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6066996/ https://www.ncbi.nlm.nih.gov/pubmed/29910124 http://dx.doi.org/10.1016/j.stemcr.2018.05.008 |
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