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

Author:

Cooke Christopher B.123ORCID,Barrington Christopher1ORCID,Baillie-Benson Peter1456ORCID,Nichols Jennifer456ORCID,Moris Naomi1ORCID

Affiliation:

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

2. University of Cambridge 2 Department of Genetics , , Cambridge CB2 3EH , UK

3. Abcam 3 , Discovery Drive, Cambridge Biomedical Campus, Cambridge CB2 0AX , UK

4. Wellcome Trust – MRC Stem Cell Institute, University of Cambridge, Jeffrey Cheah Biomedical Centre 4 , Puddicombe Way, Cambridge CB2 0AW , UK

5. University of Cambridge 5 Department of Physiology, Development and Neuroscience , , Tennis Court Road, Cambridge CB2 3EG , UK

6. Centre for Trophoblast Research, University of Cambridge 6 , Cambridge , UK

Abstract

ABSTRACT Primordial germ cells (PGCs) are the early embryonic precursors of gametes – sperm and egg cells. PGC-like cells (PGCLCs) can currently be derived in vitro from pluripotent cells exposed to signalling cocktails and aggregated into large embryonic bodies, but these do not recapitulate the native embryonic environment during PGC formation. Here, we show that mouse gastruloids, a three-dimensional in vitro model of gastrulation, contain a population of gastruloid-derived PGCLCs (Gld-PGCLCs) that resemble early PGCs in vivo. Importantly, the conserved organisation of mouse gastruloids leads to coordinated spatial and temporal localisation of Gld-PGCLCs relative to surrounding somatic cells, even in the absence of specific exogenous PGC-specific signalling or extra-embryonic tissues. In gastruloids, self-organised interactions between cells and tissues, including the endodermal epithelium, enables the specification and subsequent maturation of a pool of Gld-PGCLCs. As such, mouse gastruloids represent a new source of PGCLCs in vitro and, owing to their inherent co-development, serve as a novel model to study the dynamics of PGC development within integrated tissue environments.

Funder

Francis Crick Institute

Cancer Research UK

Medical Research Council

Wellcome Trust

Publisher

The Company of Biologists

Subject

Developmental Biology,Molecular Biology

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