Gastruloid-derived primordial germ cell-like cells develop dynamically within integrated tissues

Christopher B Cooke1,2,3, Christopher Barrington1, Peter Baillie-Benson1,4,5,6

  • 1The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.

Development (Cambridge, England)
|August 1, 2023
PubMed

Insights

Mouse gastruloids, a 3D model of gastrulation, generate primordial germ cell-like cells (PGCLCs) that mimic in vivo development. This model offers new insights into germ cell formation within natural tissue environments.

Area of Science:

  • Developmental Biology
  • Stem Cell Biology
  • Reproductive Biology

Background:

  • Primordial germ cells (PGCs) are essential for gamete formation.
  • Current in vitro methods for deriving PGC-like cells (PGCLCs) lack native embryonic context.
  • Existing models do not fully recapitulate the spatial and temporal dynamics of PGC development.

Purpose of the Study:

  • To investigate the potential of mouse gastruloids as a novel in vitro model for PGC development.
  • To characterize gastruloid-derived PGCLCs (Gld-PGCLCs) and compare them to in vivo PGCs.
  • To explore the self-organizing principles governing PGC specification within gastruloids.

Main Methods:

  • Generation of mouse gastruloids, a 3D in vitro model of gastrulation.
  • Analysis of gastruloid-derived cells for PGC markers and characteristics.
  • Comparative study of Gld-PGCLCs with in vivo PGCs.
  • Investigation of cellular interactions and tissue organization within gastruloids.

Main Results:

  • Mouse gastruloids spontaneously generate a population of Gld-PGCLCs resembling early PGCs.
  • Gld-PGCLCs exhibit coordinated spatial and temporal localization with surrounding somatic cells within gastruloids.
  • PGC specification and maturation occur through self-organized cellular and tissue interactions, independent of exogenous PGC-specific signals or extra-embryonic tissues.
  • The endodermal epithelium plays a role in Gld-PGCLC specification and maturation.

Conclusions:

  • Mouse gastruloids provide a new and valuable in vitro source of PGCLCs.
  • Gastruloids serve as a novel model for studying PGC development within integrated, self-organizing tissue environments.
  • This model system advances our understanding of the intrinsic mechanisms governing germ cell formation during early embryogenesis.

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