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Defective chromatin architectures in embryonic stem cells derived from somatic cell nuclear transfer impair their differentiation potentials

Nuclear transfer embryonic stem cells (ntESCs) hold enormous promise for individual-specific regenerative medicine. However, the chromatin states of ntESCs remain poorly characterized. In this study, we employed ATAC-seq and Hi-C techniques to explore the chromatin accessibility and three-dimensiona...

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Autores principales: Wu, Dan-Ya, Li, Xinxin, Sun, Qiao-Ran, Dou, Cheng-Li, Xu, Tian, He, Hainan, Luo, Han, Fu, Haitao, Bu, Guo-Wei, Luo, Bingbing, Zhang, Xia, Ma, Bin-Guang, Peng, Cheng, Miao, Yi-Liang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8595669/
https://www.ncbi.nlm.nih.gov/pubmed/34785659
http://dx.doi.org/10.1038/s41419-021-04384-2
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author Wu, Dan-Ya
Li, Xinxin
Sun, Qiao-Ran
Dou, Cheng-Li
Xu, Tian
He, Hainan
Luo, Han
Fu, Haitao
Bu, Guo-Wei
Luo, Bingbing
Zhang, Xia
Ma, Bin-Guang
Peng, Cheng
Miao, Yi-Liang
author_facet Wu, Dan-Ya
Li, Xinxin
Sun, Qiao-Ran
Dou, Cheng-Li
Xu, Tian
He, Hainan
Luo, Han
Fu, Haitao
Bu, Guo-Wei
Luo, Bingbing
Zhang, Xia
Ma, Bin-Guang
Peng, Cheng
Miao, Yi-Liang
author_sort Wu, Dan-Ya
collection PubMed
description Nuclear transfer embryonic stem cells (ntESCs) hold enormous promise for individual-specific regenerative medicine. However, the chromatin states of ntESCs remain poorly characterized. In this study, we employed ATAC-seq and Hi-C techniques to explore the chromatin accessibility and three-dimensional (3D) genome organization of ntESCs. The results show that the chromatin accessibility and genome structures of somatic cells are re-arranged to ESC-like states overall in ntESCs, including compartments, topologically associating domains (TADs) and chromatin loops. However, compared to fertilized ESCs (fESCs), ntESCs show some abnormal openness and structures that have not been reprogrammed completely, which impair the differentiation potential of ntESCs. The histone modification H3K9me3 may be involved in abnormal structures in ntESCs, including incorrect compartment switches and incomplete TAD rebuilding. Moreover, ntESCs and iPSCs show high similarity in 3D genome structures, while a few differences are detected due to different somatic cell origins and reprogramming mechanisms. Through systematic analyses, our study provides a global view of chromatin accessibility and 3D genome organization in ntESCs, which can further facilitate the understanding of the similarities and differences between ntESCs and fESCs.
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spelling pubmed-85956692021-11-19 Defective chromatin architectures in embryonic stem cells derived from somatic cell nuclear transfer impair their differentiation potentials Wu, Dan-Ya Li, Xinxin Sun, Qiao-Ran Dou, Cheng-Li Xu, Tian He, Hainan Luo, Han Fu, Haitao Bu, Guo-Wei Luo, Bingbing Zhang, Xia Ma, Bin-Guang Peng, Cheng Miao, Yi-Liang Cell Death Dis Article Nuclear transfer embryonic stem cells (ntESCs) hold enormous promise for individual-specific regenerative medicine. However, the chromatin states of ntESCs remain poorly characterized. In this study, we employed ATAC-seq and Hi-C techniques to explore the chromatin accessibility and three-dimensional (3D) genome organization of ntESCs. The results show that the chromatin accessibility and genome structures of somatic cells are re-arranged to ESC-like states overall in ntESCs, including compartments, topologically associating domains (TADs) and chromatin loops. However, compared to fertilized ESCs (fESCs), ntESCs show some abnormal openness and structures that have not been reprogrammed completely, which impair the differentiation potential of ntESCs. The histone modification H3K9me3 may be involved in abnormal structures in ntESCs, including incorrect compartment switches and incomplete TAD rebuilding. Moreover, ntESCs and iPSCs show high similarity in 3D genome structures, while a few differences are detected due to different somatic cell origins and reprogramming mechanisms. Through systematic analyses, our study provides a global view of chromatin accessibility and 3D genome organization in ntESCs, which can further facilitate the understanding of the similarities and differences between ntESCs and fESCs. Nature Publishing Group UK 2021-11-16 /pmc/articles/PMC8595669/ /pubmed/34785659 http://dx.doi.org/10.1038/s41419-021-04384-2 Text en © The Author(s) 2021, corrected publication 2021 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Wu, Dan-Ya
Li, Xinxin
Sun, Qiao-Ran
Dou, Cheng-Li
Xu, Tian
He, Hainan
Luo, Han
Fu, Haitao
Bu, Guo-Wei
Luo, Bingbing
Zhang, Xia
Ma, Bin-Guang
Peng, Cheng
Miao, Yi-Liang
Defective chromatin architectures in embryonic stem cells derived from somatic cell nuclear transfer impair their differentiation potentials
title Defective chromatin architectures in embryonic stem cells derived from somatic cell nuclear transfer impair their differentiation potentials
title_full Defective chromatin architectures in embryonic stem cells derived from somatic cell nuclear transfer impair their differentiation potentials
title_fullStr Defective chromatin architectures in embryonic stem cells derived from somatic cell nuclear transfer impair their differentiation potentials
title_full_unstemmed Defective chromatin architectures in embryonic stem cells derived from somatic cell nuclear transfer impair their differentiation potentials
title_short Defective chromatin architectures in embryonic stem cells derived from somatic cell nuclear transfer impair their differentiation potentials
title_sort defective chromatin architectures in embryonic stem cells derived from somatic cell nuclear transfer impair their differentiation potentials
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8595669/
https://www.ncbi.nlm.nih.gov/pubmed/34785659
http://dx.doi.org/10.1038/s41419-021-04384-2
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