OCT4 induces embryonic pluripotency via STAT3 signaling and metabolic mechanisms

Giuliano G Stirparo, Agata Kurowski, Ayaka Yanagida, Lawrence E Bates, Stanley E Strawbridge, Siarhei Hladkou, Hannah T Stuart, Thorsten E Boroviak, Jose C R Silva, Jennifer Nichols*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
JournalProceedings of the National Academy of Sciences (PNAS)
Issue number3
Publication statusPublished - 19 Jan 2021

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Blastocyst Inner Cell Mass/metabolism
  • Cell Lineage/genetics
  • Embryo, Mammalian
  • Embryonic Development/genetics
  • Gene Expression Regulation, Developmental/genetics
  • Glycolysis/genetics
  • Mice
  • Octamer Transcription Factor-3/genetics
  • Pluripotent Stem Cells/metabolism
  • STAT3 Transcription Factor/genetics
  • Signal Transduction/genetics
  • Single-Cell Analysis


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