دورية أكاديمية
The MuvB complex safeguards embryonic stem cell identity through regulation of the cell cycle machinery.
| العنوان: | The MuvB complex safeguards embryonic stem cell identity through regulation of the cell cycle machinery. |
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| المؤلفون: | Wang C; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, Medical School of Nanjing University, Nanjing, China., Hao K; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, Medical School of Nanjing University, Nanjing, China., Dong L; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, Medical School of Nanjing University, Nanjing, China., Wang J; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, Medical School of Nanjing University, Nanjing, China., Zhao L; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, Medical School of Nanjing University, Nanjing, China., Xu L; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, Medical School of Nanjing University, Nanjing, China., Xia Y; School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China., Jiang Q; Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, China., Qin J; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, Medical School of Nanjing University, Nanjing, China; Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, China. Electronic address: qinjz@nju.edu.cn. |
| المصدر: | The Journal of biological chemistry [J Biol Chem] 2022 Mar; Vol. 298 (3), pp. 101701. Date of Electronic Publication: 2022 Feb 09. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology |
| مواضيع طبية MeSH: | Cell Cycle Proteins*/genetics , Cell Cycle Proteins*/metabolism , Embryonic Stem Cells*/cytology , Embryonic Stem Cells*/metabolism, Animals ; Apoptosis/physiology ; Cell Cycle/physiology ; Cell Differentiation/physiology ; Cell Division/physiology ; Cell Line, Tumor ; G2 Phase Cell Cycle Checkpoints ; Humans ; Mice ; Transcription Factors/metabolism |
| مستخلص: | Increasing evidences indicate that unlimited capacity for self-renewal and pluripotency, two unique properties of embryonic stem cells (ESCs), are intrinsically linked to cell cycle control. However, the precise mechanisms coordinating cell fate decisions and cell cycle regulation remain to be fully explored. Here, using CRISPR/Cas9-mediated genome editing, we show that in ESCs, deficiency of components of the cell cycle regulatory MuvB complex Lin54 or Lin52, but not Lin9 or Lin37, triggers G2/M arrest, loss of pluripotency, and spontaneous differentiation. Further dissection of these phenotypes demonstrated that this cell cycle arrest is accompanied by the gradual activation of mesoendodermal lineage-specifying genes. Strikingly, the abnormalities observed in Lin54-null ESCs were partially but significantly rescued by ectopic coexpression of genes encoding G2/M proteins Cyclin B1 and Cdk1. Thus, our study provides new insights into the mechanisms by which the MuvB complex determines cell fate through regulation of the cell cycle machinery. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: G2/M; Lin37; Lin52; Lin54; Lin9; MuvB; cell cycle; embryonic stem cells; germ layer lineages; pluripotency |
| المشرفين على المادة: | 0 (Cell Cycle Proteins) 0 (Transcription Factors) |
| تواريخ الأحداث: | Date Created: 20220212 Date Completed: 20220415 Latest Revision: 20220531 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC8892154 |
| DOI: | 10.1016/j.jbc.2022.101701 |
| PMID: | 35148988 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1083-351X |
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| DOI: | 10.1016/j.jbc.2022.101701 |