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

Abstract 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-d...

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Main Authors: Dan-Ya Wu, Xinxin Li, Qiao-Ran Sun, Cheng-Li Dou, Tian Xu, Hainan He, Han Luo, Haitao Fu, Guo-Wei Bu, Bingbing Luo, Xia Zhang, Bin-Guang Ma, Cheng Peng, Yi-Liang Miao
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Language:EN
Published: Nature Publishing Group 2021
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Online Access:https://doaj.org/article/8a636afc1a2b4f8fb72815c6b5276ed8
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spelling oai:doaj.org-article:8a636afc1a2b4f8fb72815c6b5276ed82021-11-21T12:03:27ZDefective chromatin architectures in embryonic stem cells derived from somatic cell nuclear transfer impair their differentiation potentials10.1038/s41419-021-04384-22041-4889https://doaj.org/article/8a636afc1a2b4f8fb72815c6b5276ed82021-11-01T00:00:00Zhttps://doi.org/10.1038/s41419-021-04384-2https://doaj.org/toc/2041-4889Abstract 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.Dan-Ya WuXinxin LiQiao-Ran SunCheng-Li DouTian XuHainan HeHan LuoHaitao FuGuo-Wei BuBingbing LuoXia ZhangBin-Guang MaCheng PengYi-Liang MiaoNature Publishing GrouparticleCytologyQH573-671ENCell Death and Disease, Vol 12, Iss 12, Pp 1-14 (2021)
institution DOAJ
collection DOAJ
language EN
topic Cytology
QH573-671
spellingShingle Cytology
QH573-671
Dan-Ya Wu
Xinxin Li
Qiao-Ran Sun
Cheng-Li Dou
Tian Xu
Hainan He
Han Luo
Haitao Fu
Guo-Wei Bu
Bingbing Luo
Xia Zhang
Bin-Guang Ma
Cheng Peng
Yi-Liang Miao
Defective chromatin architectures in embryonic stem cells derived from somatic cell nuclear transfer impair their differentiation potentials
description Abstract 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.
format article
author Dan-Ya Wu
Xinxin Li
Qiao-Ran Sun
Cheng-Li Dou
Tian Xu
Hainan He
Han Luo
Haitao Fu
Guo-Wei Bu
Bingbing Luo
Xia Zhang
Bin-Guang Ma
Cheng Peng
Yi-Liang Miao
author_facet Dan-Ya Wu
Xinxin Li
Qiao-Ran Sun
Cheng-Li Dou
Tian Xu
Hainan He
Han Luo
Haitao Fu
Guo-Wei Bu
Bingbing Luo
Xia Zhang
Bin-Guang Ma
Cheng Peng
Yi-Liang Miao
author_sort Dan-Ya Wu
title 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_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_sort defective chromatin architectures in embryonic stem cells derived from somatic cell nuclear transfer impair their differentiation potentials
publisher Nature Publishing Group
publishDate 2021
url https://doaj.org/article/8a636afc1a2b4f8fb72815c6b5276ed8
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