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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...

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Autores principales: Liu, Qidong, Wang, Guiying, Lyu, Yao, Bai, Mingliang, Jiapaer, Zeyidan, Jia, Wenwen, Han, Tong, Weng, Rong, Yang, Yiwei, Yu, Yangyang, Kang, Jiuhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
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.
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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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