Atypical cell cycle profile of mouse embryonic stem cell is regulated by classic oncogenic and tumor suppressive genes in vitro
Embryonic stem cells (ESCs) exhibit an unusual cell cycle profile containing a short G1 phase. Whether this feature is required to maintain pluripotency is a matter of debate. Here, we report that the short G1 phase is a consequence of MEK1/2 kinase-mediated promotion of G1/S transition, but not nec...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844022032674 |
| _version_ | 1797960975305932800 |
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| author | Jinfeng Jiang Tong Qiu Chao Yang Yuan Yuan Ling Qin Peixuan Zhang |
| author_facet | Jinfeng Jiang Tong Qiu Chao Yang Yuan Yuan Ling Qin Peixuan Zhang |
| author_sort | Jinfeng Jiang |
| collection | DOAJ |
| description | Embryonic stem cells (ESCs) exhibit an unusual cell cycle profile containing a short G1 phase. Whether this feature is required to maintain pluripotency is a matter of debate. Here, we report that the short G1 phase is a consequence of MEK1/2 kinase-mediated promotion of G1/S transition, but not necessarily coupled with pluripotency maintenance. We find that compared to primed ESCs, naïve ESCs exhibit a significantly longer G1 phase due to the inhibition of MEK1/2 kinases. MEK1/2 inhibition increases intracellular level of reactive oxygen species (ROS), leading to the stabilization of p53 protein. The genetic ablation of p53 largely converts the cell cycle profile of naïve ESCs to that of primed ESCs. These results demonstrate that pluripotency and proliferation are separable cellular events, and the short G1 phase of primed ESCs is a manifestation of the intricate interplay between classical oncogenes MEK1/2 and tumor suppressor gene TP53 to promote G1/S transition. |
| first_indexed | 2024-04-11T00:52:15Z |
| format | Article |
| id | doaj.art-71b8d312b64d41cda43dade389bcc070 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-11T00:52:15Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
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| series | Heliyon |
| spelling | doaj.art-71b8d312b64d41cda43dade389bcc0702023-01-05T08:37:43ZengElsevierHeliyon2405-84402022-12-01812e11979Atypical cell cycle profile of mouse embryonic stem cell is regulated by classic oncogenic and tumor suppressive genes in vitroJinfeng Jiang0Tong Qiu1Chao Yang2Yuan Yuan3Ling Qin4Peixuan Zhang5Departments of Pediatrics and Obstetrics & Gynecology, West China Second University Hospital, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Center of Growth, Metabolism and Aging, State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu 610041, China; Frontiers Science Center for Disease-related Molecular Network, West China HospitalDepartments of Pediatrics and Obstetrics & Gynecology, West China Second University Hospital, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Center of Growth, Metabolism and Aging, State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu 610041, China; Frontiers Science Center for Disease-related Molecular Network, West China HospitalDepartments of Pediatrics and Obstetrics & Gynecology, West China Second University Hospital, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Center of Growth, Metabolism and Aging, State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu 610041, China; Frontiers Science Center for Disease-related Molecular Network, West China HospitalDivision of Bioinformatics, Sichuan Cunde Therapeutics, Chengdu 610093, ChinaDepartment of Gastroenterology, First Affiliated Hospital of Chengdu Medical College; Corresponding authors.Departments of Pediatrics and Obstetrics & Gynecology, West China Second University Hospital, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Center of Growth, Metabolism and Aging, State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu 610041, China; Corresponding authors.Embryonic stem cells (ESCs) exhibit an unusual cell cycle profile containing a short G1 phase. Whether this feature is required to maintain pluripotency is a matter of debate. Here, we report that the short G1 phase is a consequence of MEK1/2 kinase-mediated promotion of G1/S transition, but not necessarily coupled with pluripotency maintenance. We find that compared to primed ESCs, naïve ESCs exhibit a significantly longer G1 phase due to the inhibition of MEK1/2 kinases. MEK1/2 inhibition increases intracellular level of reactive oxygen species (ROS), leading to the stabilization of p53 protein. The genetic ablation of p53 largely converts the cell cycle profile of naïve ESCs to that of primed ESCs. These results demonstrate that pluripotency and proliferation are separable cellular events, and the short G1 phase of primed ESCs is a manifestation of the intricate interplay between classical oncogenes MEK1/2 and tumor suppressor gene TP53 to promote G1/S transition.http://www.sciencedirect.com/science/article/pii/S2405844022032674Cell cycleEmbryonic stem cellP53ROS |
| spellingShingle | Jinfeng Jiang Tong Qiu Chao Yang Yuan Yuan Ling Qin Peixuan Zhang Atypical cell cycle profile of mouse embryonic stem cell is regulated by classic oncogenic and tumor suppressive genes in vitro Heliyon Cell cycle Embryonic stem cell P53 ROS |
| title | Atypical cell cycle profile of mouse embryonic stem cell is regulated by classic oncogenic and tumor suppressive genes in vitro |
| title_full | Atypical cell cycle profile of mouse embryonic stem cell is regulated by classic oncogenic and tumor suppressive genes in vitro |
| title_fullStr | Atypical cell cycle profile of mouse embryonic stem cell is regulated by classic oncogenic and tumor suppressive genes in vitro |
| title_full_unstemmed | Atypical cell cycle profile of mouse embryonic stem cell is regulated by classic oncogenic and tumor suppressive genes in vitro |
| title_short | Atypical cell cycle profile of mouse embryonic stem cell is regulated by classic oncogenic and tumor suppressive genes in vitro |
| title_sort | atypical cell cycle profile of mouse embryonic stem cell is regulated by classic oncogenic and tumor suppressive genes in vitro |
| topic | Cell cycle Embryonic stem cell P53 ROS |
| url | http://www.sciencedirect.com/science/article/pii/S2405844022032674 |
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