Inhibition of pluripotency networks by the Rb tumor suppressor restricts reprogramming and tumorigenesis.
Inhibition of pluripotency networks by the Rb tumor suppressor restricts reprogramming and tumorigenesis.
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DOI：
10.1016/j.stem.2014.10.019
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发表时间：
2015-01-08
期刊：
影响因子：
23.9
通讯作者：
Wernig, Marius
中科院分区：
文献类型：
--
作者：
Kareta, Michael S.;Gorges, Laura L.;Hafeez, Sana;Benayoun, Berenice A.;Marro, Samuele;Zmoos, Anne-Flore;Cecchini, Matthew J.;Spacek, Damek;Batista, Luis F. Z.;O'Brien, Megan;Ng, Yi-Han;Ang, Cheen Euong;Vaka, Dedeepya;Artandi, Steven E.;Dick, Frederick A.;Brunet, Anne;Sage, Julien;Wernig, Marius
视网膜母细胞瘤肿瘤抑制基因Rb的突变与多种形式的人类癌症有关。在这项研究中，我们研究了在细胞重编程的背景下Rb失活的早期后果。我们发现Rb失活促进分化细胞重编程到多能状态。出乎意料的是，这种作用与细胞周期无关，而是反映了Rb与多能性基因（包括Sox2和Oct4）的直接结合，从而导致染色质状态受到抑制。更广泛地说，这种对多能性网络和Sox2的调控对于小鼠Rb缺失后肿瘤的发生至关重要。因此，这些研究确定Rb是多能性网络的全局转录抑制因子，为之前关于其参与细胞命运柔韧性的报道提供了分子基础，并暗示多能性因子如Sox2在肿瘤发生中与Rb功能丧失相关的调控错误。
Mutations in the retinoblastoma tumor suppressor gene Rb are involved in many forms of human cancer. In this study, we investigated the early consequences of inactivating Rb in the context of cellular reprogramming. We found that Rb inactivation promotes the reprogramming of differentiated cells to a pluripotent state. Unexpectedly, this effect is cell cycle independent, and instead reflects direct binding of Rb to pluripotency genes, including Sox2 and Oct4, which leads to a repressed chromatin state. More broadly, this regulation of pluripotency networks and Sox2 in particular is critical for the initiation of tumors upon loss of Rb in mice. These studies therefore identify Rb as a global transcriptional repressor of pluripotency networks, providing a molecular basis for previous reports about its involvement in cell fate pliability, and implicate misregulation of pluripotency factors such as Sox2 in tumorigenesis related to loss of Rb function.
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重编程因子表达引发了广泛的靶向染色质重塑。
影响因子：
23.9
作者：
Koche RP;Smith ZD;Adli M;Gu H;Ku M;Gnirke A;Bernstein BE;Meissner A
通讯作者：
Meissner A
影响因子：
64.8
作者：
Batista, Luis F. Z.;Pech, MatthewF.;Zhong, Franklin L.;Nguyen, Ha Nam;Xie, Kathleen T.;Zaug, Arthur J.;Crary, Sharon M.;Choi, Jinkuk;Sebastiano, Vittorio;Cherry, Athena;Giri, Neelam;Wernig, Marius;Alter, Blanche P.;Cech, Thomas R.;Savage, Sharon A.;Pera, Renee A. Reijo;Artandi, Steven E.
通讯作者：
Artandi, Steven E.
影响因子：
23.9
作者：
Li, Fang;He, Zhimin;Shen, Jingping;Huang, Qian;Li, Wenrong;Liu, Xinjian;He, Yujun;Wolf, Frank;Li, Chuan-Yuan
通讯作者：
Li, Chuan-Yuan
影响因子：
64.5
作者：
Benayoun BA;Pollina EA;Ucar D;Mahmoudi S;Karra K;Wong ED;Devarajan K;Daugherty AC;Kundaje AB;Mancini E;Hitz BC;Gupta R;Rando TA;Baker JC;Snyder MP;Cherry JM;Brunet A
通讯作者：
Brunet A
影响因子：
16
作者：
Bourgo, Ryan J.;Thangavel, Chellappagounder;Knudsen, Erik S.
通讯作者：
Knudsen, Erik S.