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Cardiopharyngeal Mesoderm specification into cardiac and skeletal muscle lineages in gastruloids

View ORCID ProfileLaurent Argiro, Céline Chevalier, View ORCID ProfileCaroline Choquet, View ORCID ProfileNitya Nandkishore, Adeline Ghata, View ORCID ProfileAnaïs Baudot, View ORCID ProfileStéphane Zaffran, View ORCID ProfileFabienne Lescroart
doi: https://doi.org/10.1101/2023.05.15.540476
Laurent Argiro
1Aix-Marseille Université, INSERM, MMG U1251, 13005 Marseille, France
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  • ORCID record for Laurent Argiro
Céline Chevalier
1Aix-Marseille Université, INSERM, MMG U1251, 13005 Marseille, France
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Caroline Choquet
1Aix-Marseille Université, INSERM, MMG U1251, 13005 Marseille, France
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Nitya Nandkishore
1Aix-Marseille Université, INSERM, MMG U1251, 13005 Marseille, France
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Adeline Ghata
1Aix-Marseille Université, INSERM, MMG U1251, 13005 Marseille, France
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Anaïs Baudot
1Aix-Marseille Université, INSERM, MMG U1251, 13005 Marseille, France
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Stéphane Zaffran
1Aix-Marseille Université, INSERM, MMG U1251, 13005 Marseille, France
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  • For correspondence: fabienne.lescroart@univ-amu.fr stephane.zaffran@univ-amu.fr
Fabienne Lescroart
1Aix-Marseille Université, INSERM, MMG U1251, 13005 Marseille, France
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  • ORCID record for Fabienne Lescroart
  • For correspondence: fabienne.lescroart@univ-amu.fr stephane.zaffran@univ-amu.fr
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Abstract

Cardiopharyngeal mesoderm contributes to the formation of the heart and head muscles. However, the mechanisms governing cardiopharyngeal mesoderm specification remain unclear. Indeed, there is a lack of an in vitro model replicating the differentiation of both heart and head muscles to study these mechanisms. Such models are required to allow live-imaging and high throughput genetic and drug screening. Here, we show that the formation of self-organizing or pseudo-embryos from mouse embryonic stem cells (mESCs), also called gastruloids, reproduces cardiopharyngeal mesoderm specification towards cardiac and skeletal muscle lineages. By conducting a comprehensive temporal analysis of cardiopharyngeal mesoderm establishment and differentiation in gastruloids and comparing it to mouse embryos, we present the first evidence for skeletal myogenesis in gastruloids. By inferring lineage trajectories from the gastruloids single-cell transcriptomic data, we further suggest that heart and head muscles formed in gastruloids derive from cardiopharyngeal mesoderm progenitors. We identify different subpopulations of cardiomyocytes and skeletal muscles, which most likely correspond to different states of myogenesis with “head-like” and “trunk-like” skeletal myoblasts. These findings unveil the potential of mESC-derived gastruloids to undergo specification into both cardiac and skeletal muscle lineages, allowing the investigation of the mechanisms of cardiopharyngeal mesoderm differentiation in development and how this could be affected in congenital diseases.

Competing Interest Statement

The authors have declared no competing interest.

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  • ↵£ co-last authors.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 15, 2023.
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Cardiopharyngeal Mesoderm specification into cardiac and skeletal muscle lineages in gastruloids
Laurent Argiro, Céline Chevalier, Caroline Choquet, Nitya Nandkishore, Adeline Ghata, Anaïs Baudot, Stéphane Zaffran, Fabienne Lescroart
bioRxiv 2023.05.15.540476; doi: https://doi.org/10.1101/2023.05.15.540476
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Cardiopharyngeal Mesoderm specification into cardiac and skeletal muscle lineages in gastruloids
Laurent Argiro, Céline Chevalier, Caroline Choquet, Nitya Nandkishore, Adeline Ghata, Anaïs Baudot, Stéphane Zaffran, Fabienne Lescroart
bioRxiv 2023.05.15.540476; doi: https://doi.org/10.1101/2023.05.15.540476

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