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DOI | 10.1073/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 |
ISSN | 00278424 |
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 |
推荐引用方式 GB/T 7714 | 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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