Germline competency of human embryonic stem cells depends on eomesodermin

Di Chen, Wanlu Liu, Anastasia Lukianchikov, Grace V. Hancock, Jill Zimmerman, Matthew G. Lowe, Rachel Kim, Zoran Galic, Naoko Irie, M. Azim Surani, Steven E. Jacobsen, Amander T. Clark

Research output: Contribution to journalArticlepeer-review

49 Citations (Scopus)

Abstract

In humans, germline competency and the specification of primordial germ cells (PGCs) are thought to occur in a restricted developmental window during early embryogenesis. Despite the importance of specifying the appropriate number of PGCs for human reproduction, the molecular mechanisms governing PGC formation remain largely unexplored. Here, we compared PGC-like cell (PGCLC) differentiation from 18 independently derived human embryonic stem cell (hESC) lines, and discovered that the expression of primitive streak genes were positively associated with hESC germline competency. Furthermore, we show that chemical inhibition of TGFß and WNT signaling, which are required for primitive streak formation and CRISPR/Cas9 deletion of Eomesodermin (EOMES), significantly impacts PGCLC differentiation from hESCs. Taken together, our results suggest that human PGC formation involves signaling and transcriptional programs associated with somatic germ layer induction and expression of EOMES.

Original languageEnglish
Pages (from-to)850-861
Number of pages12
JournalBiology of reproduction
Volume97
Issue number6
DOIs
Publication statusPublished - 2017 Dec 1
Externally publishedYes

Keywords

  • Embryonic stem cells
  • EOMES
  • Human
  • Primordial germ cells

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology

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