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

Cooke, Christopher B.; Barrington, Christopher; Baillie-Benson, Peter; Nichols, Jennifer; Moris, Naomi

doi:10.1242/dev.201790

Cited by 12 publications

(11 citation statements)

References 98 publications

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“…Developmental progression of PGCLCs into the migratory phase can be aided by co-culturing with somatic gonadal cells or hindgut ( Hwang et al, 2020 ; Yamashiro et al, 2018 ; Alves-Lopes et al, 2023 ; Oikawa et al, 2022 ). Alternatively, recent advances in the derivation of embryo models that develop through gastrulation provide a rich platform for modeling PGC migration ( Cooke et al, 2023 ; Amadei et al, 2022 ; Tarazi et al, 2022 ). Regardless of approach, these new in vitro technologies are sure to provide ample hypotheses to test in vivo .…”

Section: Conclusion Current Challenges and The Next Frontiermentioning

confidence: 99%

The journey of a generation: advances and promises in the study of primordial germ cell migration

Barton,

Roa-de la Cruz,

Lehmann

et al. 2024

Development

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The germline provides the genetic and non-genetic information that passes from one generation to the next. Given this important role in species propagation, egg and sperm precursors, called primordial germ cells (PGCs), are one of the first cell types specified during embryogenesis. In fact, PGCs form well before the bipotential somatic gonad is specified. This common feature of germline development necessitates that PGCs migrate through many tissues to reach the somatic gonad. During their journey, PGCs must respond to select environmental cues while ignoring others in a dynamically developing embryo. The complex multi-tissue, combinatorial nature of PGC migration is an excellent model for understanding how cells navigate complex environments in vivo. Here, we discuss recent findings on the migratory path, the somatic cells that shepherd PGCs, the guidance cues somatic cells provide, and the PGC response to these cues to reach the gonad and establish the germline pool for future generations. We end by discussing the fate of wayward PGCs that fail to reach the gonad in diverse species. Collectively, this field is poised to yield important insights into emerging reproductive technologies.

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Section: Conclusion Current Challenges and The Next Frontiermentioning

confidence: 99%

The journey of a generation: advances and promises in the study of primordial germ cell migration

Barton,

Roa-de la Cruz,

Lehmann

et al. 2024

Development

View full text Add to dashboard Cite

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“…Human stem cell-derived embryos which correspondingly form structures which are more akin to that of a developing human, cavitate and form amnion-like structures atop the epiblast, a hypoblast-like layer beneath the epiblast and extensive extra-embryonic mesoderm (ExM) [ 38 , 39 ]. Mouse stem cell-derived embryos, if cultured in ex utero media, are able to develop past primary gastrulation and form remarkably complex tissues including headfolds with defined forebrain and midbrain, a beating heart, a neural tube, somites, a tail bud, a gut tube, and primordial germ cell-like cells (PGC-LCs) [ 41 , 42 ]. Curiously, these structures form in the absence of exogenous ECM support suggesting that extra-embryonic tissues may be linked to embryo morphology.…”

Section: Cell Intrinsic Biochemical Dynamics May Underly Developmenta...mentioning

confidence: 99%

Interspecies control of development during mammalian gastrulation

Simpson,

Alberio

2023

Emerging Topics in Life Sciences

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Gastrulation represents a pivotal phase of development and aberrations during this period can have major consequences, from minor anatomical deviations to severe congenital defects. Animal models are used to study gastrulation, however, there is considerable morphological and molecular diversity of gastrula across mammalian species. Here, we provide an overview of the latest research on interspecies developmental control across mammals. This includes single-cell atlases of several mammalian gastrula which have enabled comparisons of the temporal and molecular dynamics of differentiation. These studies highlight conserved cell differentiation regulators and both absolute and relative differences in differentiation dynamics between species. Recent advances in in vitro culture techniques have facilitated the derivation, maintenance and differentiation of cell lines from a range of species and the creation of multi-species models of gastrulation. Gastruloids are three-dimensional aggregates capable of self-organising and recapitulating aspects of gastrulation. Such models enable species comparisons outside the confines of the embryo. We highlight recent in vitro evidence that differentiation processes such as somitogenesis and neuronal maturation scale with known in vivo differences in developmental tempo across species. This scaling is likely due to intrinsic differences in cell biochemistry. We also highlight several studies which provide examples of cell differentiation dynamics being influenced by extrinsic factors, including culture conditions, chimeric co-culture, and xenotransplantation. These collective studies underscore the complexity of gastrulation across species, highlighting the necessity of additional datasets and studies to decipher the intricate balance between intrinsic cellular programs and extrinsic signals in shaping embryogenesis.

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“…Gastruloids are a good model to study the early stages of PGC specification as they represent the embryonic gastrulation stages when PGCs are specified. The gastruloid-derived PGLCs also express Blimp1 and Stella which make the epiblast cells commit to the germ cell fate in vivo [ 62 ]. Additionally, gastruloids also display later stages of germ cell development.…”

Section: Variations Of Gastruloids and Alternative Models To Study Me...mentioning

confidence: 99%

Gastruloids — a minimalistic model to study complex developmental metabolism

Dingare,

Steventon

2023

Emerging Topics in Life Sciences

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Metabolic networks are well placed to orchestrate the coordination of multiple cellular processes associated with embryonic development such as cell growth, proliferation, differentiation and cell movement. Here, we discuss the advantages that gastruloids, aggregates of mammalian embryonic stem cells that self-assemble a rudimentary body plan, have for uncovering the instructive role of metabolic pathways play in directing developmental processes. We emphasise the importance of using such reductionist systems to link specific pathways to defined events of early mammalian development and their utility for obtaining enough material for metabolomic studies. Finally, we review the ways in which the basic gastruloid protocol can be adapted to obtain specific models of embryonic cell types, tissues and regions. Together, we propose that gastruloids are an ideal system to rapidly uncover new mechanistic links between developmental signalling pathways and metabolic networks, which can then inform precise in vivo studies to confirm their function in the embryo.

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

Cited by 12 publications

References 98 publications

The journey of a generation: advances and promises in the study of primordial germ cell migration

The journey of a generation: advances and promises in the study of primordial germ cell migration

Interspecies control of development during mammalian gastrulation

Gastruloids — a minimalistic model to study complex developmental metabolism

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