Offspring from oocytes derived from in vitro primordial germ cell-like cells in mice

Science. 2012 Nov 16;338(6109):971-5. doi: 10.1126/science.1226889. Epub 2012 Oct 4.

Abstract

Reconstitution of female germ cell development in vitro is a key challenge in reproductive biology and medicine. We show here that female (XX) embryonic stem cells and induced pluripotent stem cells in mice are induced into primordial germ cell-like cells (PGCLCs), which, when aggregated with female gonadal somatic cells as reconstituted ovaries, undergo X-reactivation, imprint erasure, and cyst formation, and exhibit meiotic potential. Upon transplantation under mouse ovarian bursa, PGCLCs in the reconstituted ovaries mature into germinal vesicle-stage oocytes, which then contribute to fertile offspring after in vitro maturation and fertilization. Our culture system serves as a robust foundation for the investigation of key properties of female germ cells, including the acquisition of totipotency, and for the reconstitution of whole female germ cell development in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Culture Techniques
  • Cell Differentiation*
  • Embryonic Stem Cells / cytology*
  • Female
  • Fertilization in Vitro
  • Induced Pluripotent Stem Cells / cytology*
  • Male
  • Mice
  • Oocytes / cytology*
  • Oocytes / transplantation
  • Oogenesis
  • Ovarian Follicle / cytology*
  • Positive Regulatory Domain I-Binding Factor 1
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transgenes

Substances

  • Dppa3 protein, mouse
  • Prdm1 protein, mouse
  • Repressor Proteins
  • Transcription Factors
  • Positive Regulatory Domain I-Binding Factor 1

Associated data

  • GEO/GSE40716