Defective chromatin architectures in embryonic stem cells derived from somatic cell nuclear transfer impair their differentiation potentials.
Defective chromatin architectures in embryonic stem cells derived from somatic cell nuclear transfer impair their differentiation potentials.
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DOI：
10.1038/s41419-021-04384-2
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发表时间：
2021-11-16
影响因子：
9
通讯作者：
Miao YL
中科院分区：
文献类型：
--
作者：
Wu DY;Li X;Sun QR;Dou CL;Xu T;He H;Luo H;Fu H;Bu GW;Luo B;Zhang X;Ma BG;Peng C;Miao YL
核移植胚胎干细胞（ntESC）为个体特异性再生医学带来了巨大的希望。然而，ntESCs的染色质状态仍然很难表征。在这项研究中，我们采用ATAC-seq和Hi-C技术来探索ntESCs的染色质可及性和三维（3D）基因组组织。结果表明，ntESCs的染色质可及性和基因组结构整体上呈现ESC样状态，包括区室、拓扑关联结构域（TADs）和染色质环。然而，与受精的胚胎干细胞（fESCs）相比，ntESCs显示出一些异常的开放性和结构，这些结构尚未完全重编程，这损害了ntESCs的分化潜力。组蛋白修饰H3 K9 me 3可能参与ntESCs中的异常结构，包括不正确的隔室开关和不完全的细胞重建。此外，ntESC和iPSC在3D基因组结构上显示出高度相似性，而由于不同的体细胞起源和重编程机制，检测到一些差异。通过系统分析，我们的研究提供了一个整体的观点，染色质可及性和三维基因组组织在ntESCs，这可以进一步促进理解之间的相似性和差异性ntESCs和fESCs。
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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DOI：
10.1016/j.tig.2015.11.001
发表时间：
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期刊：
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