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Feeders facilitate telomere maintenance and chromosomal stability of embryonic stem cells
Feeder cells like mouse embryonic fibroblasts (MEFs) have been widely applied for culture of pluripotent stem cells, but their roles remain elusive. Noticeably, ESCs cultured on the feeders display transcriptional heterogeneity. We investigated roles of feeder cells by examining the telomere mainten...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6033898/ https://www.ncbi.nlm.nih.gov/pubmed/29976922 http://dx.doi.org/10.1038/s41467-018-05038-2 |
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author | Guo, Renpeng Ye, Xiaoying Yang, Jiao Zhou, Zhongcheng Tian, Chenglei Wang, Hua Wang, Haiying Fu, Haifeng Liu, Chun Zeng, Ming Yang, Jun Liu, Lin |
author_facet | Guo, Renpeng Ye, Xiaoying Yang, Jiao Zhou, Zhongcheng Tian, Chenglei Wang, Hua Wang, Haiying Fu, Haifeng Liu, Chun Zeng, Ming Yang, Jun Liu, Lin |
author_sort | Guo, Renpeng |
collection | PubMed |
description | Feeder cells like mouse embryonic fibroblasts (MEFs) have been widely applied for culture of pluripotent stem cells, but their roles remain elusive. Noticeably, ESCs cultured on the feeders display transcriptional heterogeneity. We investigated roles of feeder cells by examining the telomere maintenance. Here we show that telomere is longer in mESCs cultured with than without the feeders. mESC cultures without MEF feeders exhibit telomere loss, chromosomal fusion, and aneuploidy with increasing passages. Notably, feeders facilitate heterogeneous transcription of 2-cell genes including Zscan4 and telomere elongation. Moreover, feeders produce Fstl1 that together with BMP4 periodically activate Zscan4. Interestingly, Zscan4 is repressed in mESCs cultured in 2i (inhibitors of Mek and Gsk3β signaling) media, associated with shorter telomeres and increased chromosome instability. These data suggest the important role of feeders in maintaining telomeres for long-term stable self-renewal and developmental pluripotency of mESCs. |
format | Online Article Text |
id | pubmed-6033898 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-60338982018-07-09 Feeders facilitate telomere maintenance and chromosomal stability of embryonic stem cells Guo, Renpeng Ye, Xiaoying Yang, Jiao Zhou, Zhongcheng Tian, Chenglei Wang, Hua Wang, Haiying Fu, Haifeng Liu, Chun Zeng, Ming Yang, Jun Liu, Lin Nat Commun Article Feeder cells like mouse embryonic fibroblasts (MEFs) have been widely applied for culture of pluripotent stem cells, but their roles remain elusive. Noticeably, ESCs cultured on the feeders display transcriptional heterogeneity. We investigated roles of feeder cells by examining the telomere maintenance. Here we show that telomere is longer in mESCs cultured with than without the feeders. mESC cultures without MEF feeders exhibit telomere loss, chromosomal fusion, and aneuploidy with increasing passages. Notably, feeders facilitate heterogeneous transcription of 2-cell genes including Zscan4 and telomere elongation. Moreover, feeders produce Fstl1 that together with BMP4 periodically activate Zscan4. Interestingly, Zscan4 is repressed in mESCs cultured in 2i (inhibitors of Mek and Gsk3β signaling) media, associated with shorter telomeres and increased chromosome instability. These data suggest the important role of feeders in maintaining telomeres for long-term stable self-renewal and developmental pluripotency of mESCs. Nature Publishing Group UK 2018-07-05 /pmc/articles/PMC6033898/ /pubmed/29976922 http://dx.doi.org/10.1038/s41467-018-05038-2 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Guo, Renpeng Ye, Xiaoying Yang, Jiao Zhou, Zhongcheng Tian, Chenglei Wang, Hua Wang, Haiying Fu, Haifeng Liu, Chun Zeng, Ming Yang, Jun Liu, Lin Feeders facilitate telomere maintenance and chromosomal stability of embryonic stem cells |
title | Feeders facilitate telomere maintenance and chromosomal stability of embryonic stem cells |
title_full | Feeders facilitate telomere maintenance and chromosomal stability of embryonic stem cells |
title_fullStr | Feeders facilitate telomere maintenance and chromosomal stability of embryonic stem cells |
title_full_unstemmed | Feeders facilitate telomere maintenance and chromosomal stability of embryonic stem cells |
title_short | Feeders facilitate telomere maintenance and chromosomal stability of embryonic stem cells |
title_sort | feeders facilitate telomere maintenance and chromosomal stability of embryonic stem cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6033898/ https://www.ncbi.nlm.nih.gov/pubmed/29976922 http://dx.doi.org/10.1038/s41467-018-05038-2 |
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