Differential repression of Otx2 underlies the capacity of NANOG and ESRRB to induce germline entry

Matúš Vojtek, Jingchao Zhang, Juanjuan Sun, Man Zhang*, Ian Chambers

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Primordial germ cells (PGCs) arise from cells of the post-implantation epiblast in response to cytokine signaling. PGC development can be recapitulated in vitro by differentiating epiblast-like cells (EpiLCs) into PGC-like cells (PGCLCs) through cytokine exposure. Interestingly, the cytokine requirement for PGCLC induction can be bypassed by enforced expression of the transcription factor (TF) NANOG. However, the underlying mechanisms are not fully elucidated. Here, we show that NANOG mediates Otx2 downregulation in the absence of cytokines and that this is essential for PGCLC induction by NANOG. Moreover, the direct NANOG target gene Esrrb, which can substitute for several NANOG functions, does not downregulate Otx2 when overexpressed in EpiLCs and cannot promote PGCLC specification. However, expression of ESRRB in Otx2+/− EpiLCs rescues emergence of PGCLCs. This study illuminates the interplay of TFs occurring at the earliest stages of PGC specification.

Original languageEnglish
Pages (from-to)35-42
Number of pages8
JournalStem Cell Reports
Volume17
Issue number1
Early online date30 Dec 2021
DOIs
Publication statusPublished - 11 Jan 2022

Keywords

  • embryonic stem cells
  • epiblast-like cells
  • Esrrb
  • germline
  • Nanog
  • Otx2
  • primordial germ cells

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