Cell cycle heterogeneity directs spontaneous 2C state entry and exit in mouse embryonic stem cells.
Cell cycle heterogeneity directs spontaneous 2C state entry and exit in mouse embryonic stem cells.
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细胞周期异质性指导小鼠胚胎干细胞自发进入和退出2C状态
DOI：
10.1016/j.stemcr.2021.09.003
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发表时间：
2021-11-09
影响因子：
5.9
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Zhu Y;Cheng C;Chen L;Zhang L;Pan H;Hou L;Sun Z;Zhang L;Fu X;Chan KY;Zhang J
小鼠胚胎干细胞（ESCs）具有细胞间异质性。少量内源性逆转录病毒激活的双细胞样细胞（2clc）自发出现。2clc是不稳定的，在没有外界刺激的情况下，它们很容易回到多能状态。为了了解这种双向转变是如何发生的，我们对分离的2clc进行了单细胞RNA测序，这些2clc经历了2c样状态的退出和重新进入，并揭示了2c样状态和多能状态之间的逐步过渡过程。在机制上，我们发现细胞周期通过调节核仁和核仁周围异染色质的组装来影响2C基因Dux的表达，在介导这些转变中发挥了重要作用。总的来说，我们的研究结果提供了esc中2c样状态进入和退出的路线图，以及细胞周期在促进这些转变中的因果作用。细胞周期参与介导ESCs和2clc之间的动态转变，G1/S期阻滞促进Dux基因座从异染色质核蛋白中逃逸，异染色质重塑参与2C激活。本文中，Jin Zhang及其同事利用单细胞RNA-seq技术发现细胞周期变化可区分2clc、ESCs和中间状态。他们发现核仁和核仁周围异染色质的细胞周期相关重塑参与了2C程序的调节。它们在2C激活和干细胞命运决定的基础领域提供了新的进展。
Mouse embryonic stem cells (ESCs) show cell-to-cell heterogeneity. A small number of two-cell-like cells (2CLCs) marked by endogenous retrovirus activation emerge spontaneously. The 2CLCs are unstable and they are prone to transiting back to the pluripotent state without extrinsic stimulus. To understand how this bidirectional transition takes place, we performed single-cell RNA sequencing on isolated 2CLCs that underwent 2C-like state exit and re-entry, and revealed a step-by-step transitional process between 2C-like and pluripotent states. Mechanistically, we found that cell cycle played an important role in mediating these transitions by regulating assembly of the nucleolus and peri-nucleolar heterochromatin to influence 2C gene Dux expression. Collectively, our findings provide a roadmap of the 2C-like state entry and exit in ESCs and also a causal role of the cell cycle in promoting these transitions. The entry to and exit from the 2C-like state showed a step-by-step roadmap Cell cycle participates in mediating dynamic transitions between ESCs and 2CLCs G1/S phase arrest facilitates the Dux locus escape from heterochromatin Nucleolus-heterochromatin remodeling is involved in 2C activation In this article, Jin Zhang and colleagues show that cell-cycle variations distinguish 2CLCs, ESCs, and the intermediate states using single-cell RNA-seq. They found that cell-cycle-associated remodeling of nucleoli and peri-nucleolar heterochromatin was involved in the regulation of the 2C program. They provide novel advances in the fundamental field of 2C activation and stem cell fate decision.
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影响因子：
11.8
作者：
Gruenheit N;Parkinson K;Brimson CA;Kuwana S;Johnson EJ;Nagayama K;Llewellyn J;Salvidge WM;Stewart B;Keller T;van Zon W;Cotter SL;Thompson CRL
通讯作者：
Thompson CRL
影响因子：
16.8
作者：
Fadloun, Anas;Le Gras, Stephanie;Torres-Padilla, Maria-Elena
通讯作者：
Torres-Padilla, Maria-Elena
影响因子：
64.5
作者：
Gonzales, Kevin Andrew Uy;Liang, Hongqing;Ng, Huck-Hui
通讯作者：
Ng, Huck-Hui
影响因子：
30.8
作者：
Guallar D;Bi X;Pardavila JA;Huang X;Saenz C;Shi X;Zhou H;Faiola F;Ding J;Haruehanroengra P;Yang F;Li D;Sanchez-Priego C;Saunders A;Pan F;Valdes VJ;Kelley K;Blanco MG;Chen L;Wang H;Sheng J;Xu M;Fidalgo M;Shen X;Wang J
通讯作者：
Wang J
影响因子：
48
作者：
Chetty, Sundari;Pagliuca, Felicia Walton;Honore, Christian;Kweudjeu, Anastasie;Rezania, Alireza;Melton, Douglas A.
通讯作者：
Melton, Douglas A.