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Cited by 100Pluripotent Stem Cells ResearchDevelopmental Biology and Gene RegulationTelomeres, Telomerase, and Senescence

Erk signaling is indispensable for genomic stability and self-renewal of mouse embryonic stem cells

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Chen, Haixia, Guo, Renpeng, Zhang, Qian, Guo, Hongchao, Yang, Meng, Wu, Zhenfeng, Gao, Shan, Liu, Lin +1 more·2015·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1516319112PMC PMC4640739
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Abstract

Significance: Signaling pathways regulate the self-renewal and differentiation of embryonic stem cells (ESCs). Suppression of Mek/Erk signaling by pharmacological inhibitors promotes self-renewal and pluripotency maintenance of mouse ESCs, supporting the prevailing view that Erk signaling is dispensable for ESC self-renewal. However, using inducible Erk knockout ESCs, we demonstrate that Erk signaling is critical for ESC self-renewal. ESCs cannot be maintained for more than four passages after Erk depletion, associated with misregulated expression of pluripotency genes, reduced proliferation rate, G1 cell-cycle arrest, increased apoptosis, rapid shortening of telomeres, and impaired genomic stability. We further demonstrate an Erk-independent function of Mek, which may explain the diverse effects of Mek inhibition and Erk knockout on ESC self-renewal.

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Authors
Chen, H., Guo, R., Zhang, Q., Guo, H., Yang, M., Wu, Z., Gao, S., Liu, L., & Chen, L.
Affiliations
  • State Key Laboratory of Medicinal Chemical Biology, Collaborative Innovation Center for Biotherapy, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Protein Sciences and College of Life Sciences, Nankai University, Tianjin 300071, China;
  • Nankai University (CN)
  • Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2015-10-19
Volume
112
Issue
44
Pages
E5936-43
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1516319112
PMC
PMC4640739
OpenAlex
W1790368590
Cited by
100
References
66
Citations by year
2026: 3 · 2025: 3 · 2024: 7 · 2023: 13 · 2022: 9 · 2021: 12 · 2020: 10 · 2019: 12 · 2018: 12 · 2017: 8 · 2016: 9 · 2015: 2
FWCI
4.49
Type
journal article
Language
en
Open access
Licence
www.pnas.org/site/misc/userlicense.xhtml (vor, 183 d)
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (31271547 and 31470081, 31271587)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
Keywords
ERK signaling, MEK/ERK signaling, mouse embryonic stem cells, self-renewal, genome stability, telomere maintenance, telomere shortening, pluripotency genes, G1 cell cycle arrest, apoptosis, cell proliferation, differentiation genes
MeSH terms
Nanog Homeobox Protein, Animals, Cell Cycle, Signal Transduction, Telomere, Cell Death, Mice, Knockout, Homeodomain Proteins, Genomic Instability, Extracellular Signal-Regulated MAP Kinases, Mice, Embryonic Stem Cells

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