beta-Catenin safeguards the ground state of mouse pluripotency by strengthening the robustness of the transcriptional apparatus

Zhang, Meng1,2,3,4,5,6,7; Lai, Yiwei1,2,3,4,5,6,7; Krupalnik, Vladislav8; Guo, Pengcheng1,2,3,6,7,9; Guo, Xiangpeng1,2,3,5,6,7; Zhou, Jianguo1,2,3,6,7; Xu, Yan1,2,3; Yu, Zhijun1,2,3; Liu, Longqi1,2,3; Jiang, Ao10; Li, Wenjuan5,6,7,11; Ma, Gang2,3,12; Li, Na1,2,3,6,7; Fu, Xiuling13; Lv, Yuan1,2,3,4,6,7; Jiang, Mengling1,2,3,6,7; Tariq, Muqddas1,2,3,4,6,7; Kanwal, Shahzina1,2,3,6,7; Liu, Hao1,2,3,6,7; Xu, Xueting2,3,12; Zhang, Hui2,3,5,12; Huang, Yinghua2,3,5,12; Wang, Lulu2,3,4,5,12; Chen, Shuhan1,2,3,4,6,7; Babarinde, Isaac A.13; Luo, Zhiwei5,6,7,11; Wang, Dongye1,2,3,6,7; Zhou, Tiantian14; Ward, Carl1,2,3,5,6,7; He, Minghui15; Ibanez, David P.1,2,3,4,6,7; Li, Yunpan1,2,3,6,7; Zhou, Jiajian16; Yuan, Jie16; Feng, Yayan17; Arumugam, Karthik18,19; Di Vicino, Umberto18,19; Bao, Xichen1,2,3,5; Wu, Guangming5; Schambach, Axel20,21; Wang, Huating22; Sun, Hao16; Gao, Fei17,23; Qin, Baoming2,3,5,6,7,12; Hutchins, Andrew P.13; Doble, Bradley W.24,25; Hartmann, Christine26; Cosma, Maria Pia2,3,5,18,19,27; Qin, Yan4,28,29; Xu, Guo-Liang14,30; Chen, Runsheng28; Volpe, Giacomo1,2,3,5,6,7; Chen, Liang10; Hanna, Jacob H.8; Esteban, Miguel A.1,2,3,5,6,7,31

2020-07

10.1126/sciadv.aba1593

Science Advances   影响因子和分区

2375-2548

Mouse embryonic stem cells cultured with MEK (mitogen-activated protein kinase kinase) and GSK3 (glycogen synthase kinase 3) inhibitors (2i) more closely resemble the inner cell mass of preimplantation blastocysts than those cultured with SL [serum/leukemia inhibitory factor (LIF)]. The transcriptional mechanisms governing this pluripotent ground state are unresolved. Release of promoter-proximal paused RNA polymerase II (Pol2) is a multistep process necessary for pluripotency and cell cycle gene transcription in SL. We show that B-catenin, stabilized by GSK3 inhibition in medium with 2i, supplies transcriptional coregulators at pluripotency loci. This selectively strengthens pluripotency loci and renders them addicted to transcription initiation for productive gene body elongation in detriment to Pol2 pause release. By contrast, cell cycle genes are not bound by beta-catenin, and proliferation/self-renewal remains tightly controlled by Pol2 pause release under 2i conditions. Our findings explain how pluripotency is reinforced in the ground state and also provide a general model for transcriptional resilience/adaptation upon network perturbation in other contexts.

SCI ; EI

英语

NI论文

其他

National Key Research and Development Program of China[2016YFA0100102][2016YFA0100701][2016YFA0100300][2018YFA0106903] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA16030502] ; National Natural Science Foundation of China[31671537][31571524][31501192][31430049][31850410463][31970619][31950410553][31900617] ; Guangdong Province Science and Technology Program[2014A030312001][2015A030308007][2016B030229007][2016A050503037][2017B050506007] ; Guangzhou Science and Technology Program[201807010066] ; Innovative Team Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory[2018GZR110103001] ; Science and Technology Planning Project of Guangdong Province, China[2017B030314056] ; Deutsche Forschungsgemeinschaft[SFB738]

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:000552227800011

AMER ASSOC ADVANCEMENT SCIENCE

20203709157357

Transcription ; Cytology ; Stem cells ; Enzymes

Biological Materials and Tissue Engineering:461.2 ; Biology:461.9

Web of Science

1.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Lab Integrat Biol, Guangzhou 510530, Guangdong, Peoples R China
2.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, CAS Key Lab Regenerat Biol, Guangzhou 510530, Guangdong, Peoples R China
3.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangdong Prov Key Lab Stem Cells & Regenerat Med, Guangzhou 510530, Guangdong, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
5.Guangzhou Regenerat Med & Hlth Guangdong Lab, Guangzhou 510005, Peoples R China
6.Guangzhou Med Univ, Joint Sch Life Sci, Guangzhou 511436, Peoples R China
7.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangzhou 511436, Peoples R China
8.Weizmann Inst Sci, Dept Mol Genet, IL-7610001 Rehovot, Israel
9.Jilin Univ, Coll Vet Med, Changchun 130062, Peoples R China
10.Wuhan Univ, Coll Life Sci, Hubei Key Lab Cell Homeostasis, Wuhan 430072, Peoples R China
11.Guangzhou Med Univ, Guangzhou 511436, Peoples R China
12.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Lab Metab & Cell Fate, Guangzhou 510530, Guangdong, Peoples R China
13.Southern Univ Sci & Technol, Dept Biol, Shenzhen 518055, Peoples R China
14.Chinese Acad Sci, Ctr Excellence Mol Cell Sci, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci,State Key Lab Mol Biol, Shanghai 200031, Peoples R China
15.Forevergen Biosci Ctr, Guangzhou 510000, Peoples R China
16.Chinese Univ Hong Kong, Prince Wales Hosp, Li Ka Shing Inst Hlth Sci, Dept Chem Pathol, Hong Kong, Peoples R China
17.Chinese Acad Agr Sci, Agr Genom Inst Shenzhen, Genome Anal Lab, Minist Agr, Shenzhen 518120, Peoples R China
18.Barcelona Inst Sci & Technol, Ctr Genom Regulat CRG, Barcelona 08003, Spain
19.Univ Pompeu Fabra UPF, Barcelona 08003, Spain
20.Inst Expt Hematol, Hannover Med Sch, D-30625 Hannover, Germany
21.Harvard Med Sch, Boston Childrens Hosp, Div Hematol & Oncol, Boston, MA 02215 USA
22.Chinese Univ Hong Kong, Prince Wales Hosp, Li Ka Shing Inst Hlth Sci, Dept Orthopaed & Traumatol, Hong Kong, Peoples R China
23.Univ Copenhagen, Fac Hlth & Med Sci, Dept Vet & Anim Sci, Comparat Pediat & Nutr, DK-1870 Frederiksberg C, Denmark
24.Univ Manitoba, Dept Pediat & Child Hlth, Max Rady Coll Med, Rady Fac Hlth Sci, Winnipeg, MB R3E 0W2, Canada
25.Univ Manitoba, Dept Biochem & Med Genet, Max Rady Coll Med, Rady Fac Hlth Sci, Winnipeg, MB R3E 0W2, Canada
26.Univ Munster, Inst Musculoskeletal Med, Dept Bone & Skeletal Res, Med Fac, D-48149 Munster, Germany
27.Inst Catalana Recerca & Estudis Avancats ICREA, Barcelona 08003, Spain
28.Chinese Acad Sci, Inst Biophys, Key Lab RNA Biol, Beijing 100101, Peoples R China
29.Chinese Acad Sci, CAS Ctr Excellence Biomacromol, Inst Biophys, Key Lab RNA Biol, Beijing 100101, Peoples R China
30.Fudan Univ, Inst Biomed Sci, Lab Metab & Epigenet, Med Coll, Shanghai 200032, Peoples R China
31.Chinese Acad Sci, Inst Stem Cells & Regenerat, Beijing 100101, Peoples R China

Zhang, Meng,Lai, Yiwei,Krupalnik, Vladislav,et al. beta-Catenin safeguards the ground state of mouse pluripotency by strengthening the robustness of the transcriptional apparatus[J]. Science Advances,2020,6(29).

Zhang, Meng.,Lai, Yiwei.,Krupalnik, Vladislav.,Guo, Pengcheng.,Guo, Xiangpeng.,...&Esteban, Miguel A..(2020).beta-Catenin safeguards the ground state of mouse pluripotency by strengthening the robustness of the transcriptional apparatus.Science Advances,6(29).

Zhang, Meng,et al."beta-Catenin safeguards the ground state of mouse pluripotency by strengthening the robustness of the transcriptional apparatus".Science Advances 6.29(2020).