小柯机器人

中山大学丁俊军团队发现，OCT4的相分离控制TAD重组从而促进细胞命运转变。该研究于2021年5月25日在线发表于国际一流学术期刊《细胞—干细胞》。

研究人员发现，在体细胞重编程过程中存在广泛的拓扑相关域（TAD）重组，这与基因转录和细胞身份的变化有关。操纵TAD重组可促进重编程，而OCT4相分离冷凝物中浓缩的染色质环动力学有助于TAD重组。破坏OCT4相分离会减弱TAD重组和重编程，可通过将固有无序区（IDR）与OCT4融合来挽救。研究人员开发了一种称为TAD基于重组的多组学分析（TADMAN）方法，可识别重编程的调控因子。总之，这些发现阐明了在细胞重编程中受OCT4相分离调节的TAD重组作用和机制。

据了解，尽管在细胞分化过程中已观察到一些TAD重组，但TAD被认为在各种细胞类型中相对稳定。然而，关于TAD重组影响细胞命运的机制或在细胞命运转变过程中核心转录因子如何影响TAD结构仍了解很少。

附：英文原文

Title: Phase separation of OCT4 controls TAD reorganization to promote cell fate transitions

Author: Jia Wang, Haopeng Yu, Qian Ma, Pengguihang Zeng, Danya Wu, Yingping Hou, Xinyi Liu, Lumeng Jia, Jun Sun, Yilong Chen, Diana Guallar, Miguel Fidalgo, Jiahao Chen, Yangyinhui Yu, Shaoshuai Jiang, Fenjie Li, Cai Zhao, Xianglin Huang, Jianlong Wang, Cheng Li, Yujie Sun, Xiaoxi Zeng, Wei Zhang, Yiliang Miao, Junjun Ding

Issue&Volume: 2021-05-25

Abstract: Topological-associated domains (TADs) are thought to be relatively stable across celltypes, although some TAD reorganization has been observed during cellular differentiation.However, little is known about the mechanisms through which TAD reorganization affectscell fate or how master transcription factors affect TAD structures during cell fatetransitions. Here, we show extensive TAD reorganization during somatic cell reprogramming,which is correlated with gene transcription and changes in cellular identity. ManipulatingTAD reorganization promotes reprogramming, and the dynamics of concentrated chromatinloops in OCT4 phase separated condensates contribute to TAD reorganization. DisruptingOCT4 phase separation attenuates TAD reorganization and reprogramming, which can berescued by fusing an intrinsically disordered region (IDR) to OCT4. We developed anapproach termed TAD reorganization-based multiomics analysis (TADMAN), which identifiedreprogramming regulators. Together, these findings elucidate a role and mechanismof TAD reorganization, regulated by OCT4 phase separation, in cellular reprogramming.

DOI: 10.1016/j.stem.2021.04.023

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(21)00181-8

Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：25.269
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