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DOI10.1073/PNAS.2008890118
OCT4 induces embryonic pluripotency via STAT3 signaling and metabolic mechanisms
Stirparo G.G.; Kurowski A.; Yanagida A.; Bates L.E.; Strawbridge S.E.; Hladkou S.; Stuart H.T.; Boroviak T.E.; Silva J.C.R.; Nichols J.
发表日期2021
ISSN00278424
卷号118期号:3
英文摘要OCT4 is a fundamental component of the molecular circuitry governing pluripotency in vivo and in vitro. To determine how OCT4 establishes and protects the pluripotent lineage in the embryo, we used comparative single-cell transcriptomics and quantitative immunofluorescence on control and OCT4 null blastocyst inner cell masses at two developmental stages. Surprisingly, activation of most pluripotency-associated transcription factors in the early mouse embryo occurs independently of OCT4, with the exception of the JAK/STAT signaling machinery. Concurrently, OCT4 null inner cell masses ectopically activate a subset of trophectoderm-associated genes. Inspection of metabolic pathways implicates the regulation of rate-limiting glycolytic enzymes by OCT4, consistent with a role in sustaining glycolysis. Furthermore, up-regulation of the lysosomal pathway was specifically detected in OCT4 null embryos. This finding implicates a requirement for OCT4 in the production of normal trophectoderm. Collectively, our findings uncover regulation of cellular metabolism and biophysical properties as mechanisms by which OCT4 instructs pluripotency. © 2021 National Academy of Sciences. All rights reserved.
英文关键词Developmental biology; Metabolism; OCT4; Single-cell profiling; STAT3 pathway
语种英语
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/181003
作者单位Wellcome Trust-Medical Research Council Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, CB2 0AW, United Kingdom; Living Systems Institute, University of Exeter, Exeter, EX4 4QD, United Kingdom; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States; Department of Biochemistry, University of Cambridge, Cambridge, CB2 1GA, United Kingdom; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3EG, United Kingdom; Centre for Trophoblast Research, University of Cambridge, Cambridge, CB2 3EG, United Kingdom
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Stirparo G.G.,Kurowski A.,Yanagida A.,et al. OCT4 induces embryonic pluripotency via STAT3 signaling and metabolic mechanisms[J],2021,118(3).
APA Stirparo G.G..,Kurowski A..,Yanagida A..,Bates L.E..,Strawbridge S.E..,...&Nichols J..(2021).OCT4 induces embryonic pluripotency via STAT3 signaling and metabolic mechanisms.Proceedings of the National Academy of Sciences of the United States of America,118(3).
MLA Stirparo G.G.,et al."OCT4 induces embryonic pluripotency via STAT3 signaling and metabolic mechanisms".Proceedings of the National Academy of Sciences of the United States of America 118.3(2021).
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