Germline competency of human embryonic stem cells depends on eomesodermin

Biol Reprod. 2017 Jan 1;97(6):850-861. doi: 10.1093/biolre/iox138.

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 TGFβ 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.

Keywords: EOMES; embryonic stem cells; human; primordial germ cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CRISPR-Cas Systems
  • Cell Differentiation*
  • Cell Line
  • Female
  • Gene Expression Regulation, Developmental
  • Germ Cells / cytology*
  • Human Embryonic Stem Cells / cytology*
  • Humans
  • Male
  • Sequence Analysis, RNA
  • Signal Transduction*
  • T-Box Domain Proteins / physiology

Substances

  • EOMES protein, human
  • T-Box Domain Proteins