Telomere-dependent and telomere-independent roles of RAP1 in regulating human stem cell homeostasis

RAP1 is a well-known telomere-binding protein, but its functions in human stem cells have remained unclear. Here we generated RAP1-deficient human embryonic stem cells (hESCs) by using CRISPR/Cas9 technique and obtained RAP1-deficient human mesenchymal stem cells (hMSCs) and neural stem cells (hNSCs...

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Autores principales: Zhang, Xing, Liu, Zunpeng, Liu, Xiaoqian, Wang, Si, Zhang, Yiyuan, He, Xiaojuan, Sun, Shuhui, Ma, Shuai, Shyh-Chang, Ng, Liu, Feng, Wang, Qiang, Wang, Xiaoqun, Liu, Lin, Zhang, Weiqi, Song, Moshi, Liu, Guang-Hui, Qu, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Higher Education Press 2019
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6711945/
https://www.ncbi.nlm.nih.gov/pubmed/30796637
http://dx.doi.org/10.1007/s13238-019-0610-7
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author Zhang, Xing
Liu, Zunpeng
Liu, Xiaoqian
Wang, Si
Zhang, Yiyuan
He, Xiaojuan
Sun, Shuhui
Ma, Shuai
Shyh-Chang, Ng
Liu, Feng
Wang, Qiang
Wang, Xiaoqun
Liu, Lin
Zhang, Weiqi
Song, Moshi
Liu, Guang-Hui
Qu, Jing
author_facet Zhang, Xing
Liu, Zunpeng
Liu, Xiaoqian
Wang, Si
Zhang, Yiyuan
He, Xiaojuan
Sun, Shuhui
Ma, Shuai
Shyh-Chang, Ng
Liu, Feng
Wang, Qiang
Wang, Xiaoqun
Liu, Lin
Zhang, Weiqi
Song, Moshi
Liu, Guang-Hui
Qu, Jing
author_sort Zhang, Xing
collection PubMed
description RAP1 is a well-known telomere-binding protein, but its functions in human stem cells have remained unclear. Here we generated RAP1-deficient human embryonic stem cells (hESCs) by using CRISPR/Cas9 technique and obtained RAP1-deficient human mesenchymal stem cells (hMSCs) and neural stem cells (hNSCs) via directed differentiation. In both hMSCs and hNSCs, RAP1 not only negatively regulated telomere length but also acted as a transcriptional regulator of RELN by tuning the methylation status of its gene promoter. RAP1 deficiency enhanced self-renewal and delayed senescence in hMSCs, but not in hNSCs, suggesting complicated lineage-specific effects of RAP1 in adult stem cells. Altogether, these results demonstrate for the first time that RAP1 plays both telomeric and nontelomeric roles in regulating human stem cell homeostasis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13238-019-0610-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-67119452019-09-13 Telomere-dependent and telomere-independent roles of RAP1 in regulating human stem cell homeostasis Zhang, Xing Liu, Zunpeng Liu, Xiaoqian Wang, Si Zhang, Yiyuan He, Xiaojuan Sun, Shuhui Ma, Shuai Shyh-Chang, Ng Liu, Feng Wang, Qiang Wang, Xiaoqun Liu, Lin Zhang, Weiqi Song, Moshi Liu, Guang-Hui Qu, Jing Protein Cell Research Article RAP1 is a well-known telomere-binding protein, but its functions in human stem cells have remained unclear. Here we generated RAP1-deficient human embryonic stem cells (hESCs) by using CRISPR/Cas9 technique and obtained RAP1-deficient human mesenchymal stem cells (hMSCs) and neural stem cells (hNSCs) via directed differentiation. In both hMSCs and hNSCs, RAP1 not only negatively regulated telomere length but also acted as a transcriptional regulator of RELN by tuning the methylation status of its gene promoter. RAP1 deficiency enhanced self-renewal and delayed senescence in hMSCs, but not in hNSCs, suggesting complicated lineage-specific effects of RAP1 in adult stem cells. Altogether, these results demonstrate for the first time that RAP1 plays both telomeric and nontelomeric roles in regulating human stem cell homeostasis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13238-019-0610-7) contains supplementary material, which is available to authorized users. Higher Education Press 2019-02-22 2019-09 /pmc/articles/PMC6711945/ /pubmed/30796637 http://dx.doi.org/10.1007/s13238-019-0610-7 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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.
spellingShingle Research Article
Zhang, Xing
Liu, Zunpeng
Liu, Xiaoqian
Wang, Si
Zhang, Yiyuan
He, Xiaojuan
Sun, Shuhui
Ma, Shuai
Shyh-Chang, Ng
Liu, Feng
Wang, Qiang
Wang, Xiaoqun
Liu, Lin
Zhang, Weiqi
Song, Moshi
Liu, Guang-Hui
Qu, Jing
Telomere-dependent and telomere-independent roles of RAP1 in regulating human stem cell homeostasis
title Telomere-dependent and telomere-independent roles of RAP1 in regulating human stem cell homeostasis
title_full Telomere-dependent and telomere-independent roles of RAP1 in regulating human stem cell homeostasis
title_fullStr Telomere-dependent and telomere-independent roles of RAP1 in regulating human stem cell homeostasis
title_full_unstemmed Telomere-dependent and telomere-independent roles of RAP1 in regulating human stem cell homeostasis
title_short Telomere-dependent and telomere-independent roles of RAP1 in regulating human stem cell homeostasis
title_sort telomere-dependent and telomere-independent roles of rap1 in regulating human stem cell homeostasis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6711945/
https://www.ncbi.nlm.nih.gov/pubmed/30796637
http://dx.doi.org/10.1007/s13238-019-0610-7
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