Suppression of the SOX2 neural effector gene by PRDM1 promotes human germ cell fate in embryonic stem cells

Stem Cell Reports. 2014 Jan 23;2(2):189-204. doi: 10.1016/j.stemcr.2013.12.009. eCollection 2014 Feb 11.


The mechanisms of transcriptional regulation underlying human primordial germ cell (PGC) differentiation are largely unknown. The transcriptional repressor Prdm1/Blimp-1 is known to play a critical role in controlling germ cell specification in mice. Here, we show that PRDM1 is expressed in developing human gonads and contributes to the determination of germline versus neural fate in early development. We show that knockdown of PRDM1 in human embryonic stem cells (hESCs) impairs germline potential and upregulates neural genes. Conversely, ectopic expression of PRDM1 in hESCs promotes the generation of cells that exhibit phenotypic and transcriptomic features of early PGCs. Furthermore, PRDM1 suppresses transcription of SOX2. Overexpression of SOX2 in hESCs under conditions favoring germline differentiation skews cell fate from the germline to the neural lineage. Collectively, our results demonstrate that PRDM1 serves as a molecular switch to modulate the divergence of neural or germline fates through repression of SOX2 during human development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Morphogenetic Protein 4 / metabolism
  • Cell Differentiation / genetics
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / metabolism*
  • Fetus / embryology
  • Fetus / metabolism
  • Gene Expression Regulation, Developmental*
  • Germ Cells / cytology*
  • Germ Cells / metabolism*
  • Gonads / embryology
  • Gonads / metabolism
  • Humans
  • Models, Biological
  • Positive Regulatory Domain I-Binding Factor 1
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • SOXB1 Transcription Factors / genetics*
  • Wnt3A Protein / metabolism


  • Bone Morphogenetic Protein 4
  • Repressor Proteins
  • SOXB1 Transcription Factors
  • Wnt3A Protein
  • PRDM1 protein, human
  • Positive Regulatory Domain I-Binding Factor 1