Functional redundancy among Polycomb complexes in maintaining the pluripotent state of embryonic stem cells.
Functional redundancy among Polycomb complexes in maintaining the pluripotent state of embryonic stem cells.
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DOI：
10.1016/j.stemcr.2022.02.020
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发表时间：
2022-05-10
影响因子：
5.9
通讯作者：
Qin, Jinzhong
中科院分区：
文献类型：
--
作者：
Zhu, Yaru;Dong, Lixia;Wang, Congcong;Hao, Kunying;Wang, Jingnan;Zhao, Linchun;Xu, Lijun;Xia, Yin;Jiang, Qing;Qin, Jinzhong
Polycomb组蛋白组装成多蛋白复合物，称为Polycomb抑制复合物1和2（PRC 1和PRC 2），在胚胎发育期间指导细胞命运决定。PRC 1形成了一系列生物化学上不同的典型PRC 1（cPRC 1）或非典型PRC 1（ncPRC 1）复合物，其特征在于相互排斥的PCGF（PCGF 1-PCGF 6）旁亚基的存在;然而，这些亚复合物中的每一个是否实现了不同的作用仍然存在很大争议。在这里，通过在胚胎干细胞（ESC）中进行基于CRISPR的功能丧失筛选，我们发现了PRC 1亚复合物中以前未被重视的功能冗余。破坏ncPRC 1，而不是cPRC 1，显示ESC多能性的严重缺陷。值得注意的是，在ESC中非典型和典型PRC 1的共消融导致了在非典型PRC 1缺失ESC中观察到的表型的恶化，突出了PRC 1亚复合物之间的功能冗余的重要性。总之，我们的研究表明，PRC 1亚复合物冗余地沉默谱系特异性基因，并确保ESC身份的稳健维持。cPRC 1复合物不是ESC自我更新和多能性的关键决定因素ncPRC 1复合物在维持ESC的多能性中起着基本和冗余的作用cPRC 1和ncPRC 1冗余地抑制谱系特异性基因并保持ESC身份多梳组（PcG）蛋白在维持胚胎干细胞（ESC）的多能性和细胞命运决定中起着关键作用，然而，其内在机制仍然难以捉摸。Yaru等人报道Polycomb抑制复合物1（PRC 1）家族复合物在ESC多能状态的维持中具有冗余但重要的作用。
Polycomb group proteins assemble into multi-protein complexes, known as Polycomb repressive complexes 1 and 2 (PRC1 and PRC2), that guide cell fate decisions during embryonic development. PRC1 forms an array of biochemically distinct canonical PRC1 (cPRC1) or non-canonical PRC1 (ncPRC1) complexes characterized by the mutually exclusive presence of PCGF (PCGF1-PCGF6) paralog subunit; however, whether each one of these subcomplexes fulfills a distinct role remains largely controversial. Here, by performing a CRISPR-based loss-of-function screen in embryonic stem cells (ESCs), we uncovered a previously unappreciated functional redundancy among PRC1 subcomplexes. Disruption of ncPRC1, but not cPRC1, displayed severe defects in ESC pluripotency. Remarkably, coablation of non-canonical and canonical PRC1 in ESCs resulted in exacerbation of the phenotype observed in the non-canonical PRC1-null ESCs, highlighting the importance of functional redundancy among PRC1 subcomplexes. Together, our studies demonstrate that PRC1 subcomplexes act redundantly to silence lineage-specific genes and ensure robust maintenance of ESC identity. cPRC1 complexes are not the key determinant of self-renewal and pluripotency in ESCs ncPRC1 complexes play a fundamental and redundant role in maintaining pluripotency in ESCs cPRC1 and ncPRC1 act redundantly to suppress lineage-specific genes and preserve ESC identity Polycomb group (PcG) proteins play a critical role both in maintaining pluripotency and the cell fate decision of embryonic stem cells (ESCs), yet the underlying mechanisms remain elusive. Yaru et al. report that Polycomb repressive complex 1 (PRC1) family complexes share a redundant but essential role in the maintenance of the pluripotent state in ESCs.
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DOI：
10.1126/science.aal2512
发表时间：
2017-06-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Almeida M;Pintacuda G;Masui O;Koseki Y;Gdula M;Cerase A;Brown D;Mould A;Innocent C;Nakayama M;Schermelleh L;Nesterova TB;Koseki H;Brockdorff N
通讯作者：
Brockdorff N
影响因子：
23.9
作者：
Qin, Jinzhong;Whyte, Warren A.;Anderssen, Endre;Apostolou, Effie;Chen, Hsu-Hsin;Akbarian, Schahram;Bronson, Roderick T.;Hochedlinger, Konrad;Ramaswamy, Sridhar;Young, Richard A.;Hock, Hanno
通讯作者：
Hock, Hanno
影响因子：
64.5
作者：
Shao, ZH;Raible, F;Kingston, RE
通讯作者：
Kingston, RE
影响因子：
23.9
作者：
Morey, Lluis;Santanach, Alexandra;Di Croce, Luciano
通讯作者：
Di Croce, Luciano
DOI：
10.1073/pnas.0434312100
发表时间：
2003-03-04
影响因子：
11.1
作者：
Voncken, JW;Roelen, BAJ;van Lohuizen, M
通讯作者：
van Lohuizen, M