SOX17 is a critical specifier of human primordial germ cell fate

Cell. 2015 Jan 15;160(1-2):253-68. doi: 10.1016/j.cell.2014.12.013. Epub 2014 Dec 24.

Abstract

Specification of primordial germ cells (PGCs) marks the beginning of the totipotent state. However, without a tractable experimental model, the mechanism of human PGC (hPGC) specification remains unclear. Here, we demonstrate specification of hPGC-like cells (hPGCLCs) from germline competent pluripotent stem cells. The characteristics of hPGCLCs are consistent with the embryonic hPGCs and a germline seminoma that share a CD38 cell-surface marker, which collectively defines likely progression of the early human germline. Remarkably, SOX17 is the key regulator of hPGC-like fate, whereas BLIMP1 represses endodermal and other somatic genes during specification of hPGCLCs. Notable mechanistic differences between mouse and human PGC specification could be attributed to their divergent embryonic development and pluripotent states, which might affect other early cell-fate decisions. We have established a foundation for future studies on resetting of the epigenome in hPGCLCs and hPGCs for totipotency and the transmission of genetic and epigenetic information.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase 1 / metabolism
  • Animals
  • Cell Differentiation*
  • Cell Line, Tumor
  • Embryoid Bodies / metabolism
  • Embryonic Stem Cells / metabolism
  • Epigenesis, Genetic
  • Germ Cells / cytology*
  • Germ Cells / metabolism
  • Humans
  • Induced Pluripotent Stem Cells / metabolism
  • Mice
  • Positive Regulatory Domain I-Binding Factor 1
  • Repressor Proteins / metabolism
  • SOXF Transcription Factors / metabolism*
  • Seminoma / metabolism
  • Sequence Analysis, RNA

Substances

  • Repressor Proteins
  • SOX17 protein, human
  • SOXF Transcription Factors
  • PRDM1 protein, human
  • Positive Regulatory Domain I-Binding Factor 1
  • ADP-ribosyl Cyclase 1

Associated data

  • GEO/GSE60138