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OCT4 induces embryonic pluripotency via STAT3 signaling and metabolic mechanisms [Developmental Biology]
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.4 ) Pub Date : 2021-01-19 , DOI: 10.1073/pnas.2008890118
Giuliano G Stirparo 1, 2 , Agata Kurowski 3, 4 , Ayaka Yanagida 2, 3 , Lawrence E Bates 3, 5 , Stanley E Strawbridge 3 , Siarhei Hladkou 3, 5 , Hannah T Stuart 3 , Thorsten E Boroviak 6, 7 , Jose C R Silva 3, 5 , Jennifer Nichols 1, 6, 7
Affiliation  

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.



中文翻译:


OCT4 通过 STAT3 信号传导和代谢机制诱导胚胎多能性 [发育生物学]



OCT4 是控制体内和体外多能性的分子电路的基本组成部分。为了确定 OCT4 如何在胚胎中建立和保护多能谱系,我们对两个发育阶段的对照和 OCT4 缺失囊胚内细胞团使用了比较单细胞转录组学和定量免疫荧光。令人惊讶的是,除了 JAK/STAT 信号机制外,早期小鼠胚胎中大多数多能性相关转录因子的激活独立于 OCT4 发生。同时,OCT4 无效的内细胞团异位激活滋养外胚层相关基因的子集。对代谢途径的检查表明 OCT4 对限速糖酵解酶的调节,这与维持糖酵解的作用一致。此外,在 OCT4 无效胚胎中特别检测到溶酶体途径的上调。这一发现表明正常滋养外胚层的产生需要 OCT4。总的来说,我们的研究结果揭示了细胞代谢和生物物理特性的调节是 OCT4 指导多能性的机制。

更新日期:2021-01-15
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