Precise and scalable self-organization in mammalian pseudo-embryos

Mélody Merle; Leah Friedman; Corinne Chureau; Armin Shoushtarizadeh; Thomas Gregor

doi:10.1038/s41594-024-01251-4

Precise and scalable self-organization in mammalian pseudo-embryos

Mélody Merle, Leah Friedman, Corinne Chureau, Armin Shoushtarizadeh, Thomas Gregor

Princeton University

Research output: Contribution to journal › Article › peer-review

Abstract

Gene expression is inherently noisy, posing a challenge to understanding how precise and reproducible patterns of gene expression emerge in mammals. Here we investigate this phenomenon using gastruloids, a three-dimensional in vitro model for early mammalian development. Our study reveals intrinsic reproducibility in the self-organization of gastruloids, encompassing growth dynamics and gene expression patterns. We observe a remarkable degree of control over gene expression along the main body axis, with pattern boundaries positioned with single-cell precision. Furthermore, as gastruloids grow, both their physical proportions and gene expression patterns scale proportionally with system size. Notably, these properties emerge spontaneously in self-organizing cell aggregates, distinct from many in vivo systems constrained by fixed boundary conditions. Our findings shed light on the intricacies of developmental precision, reproducibility and size scaling within a mammalian system, suggesting that these phenomena might constitute fundamental features of multicellularity.

Original language	American English
Pages (from-to)	896-902
Number of pages	7
Journal	Nature Structural and Molecular Biology
Volume	31
Issue number	6
DOIs	https://doi.org/10.1038/s41594-024-01251-4
State	Published - Jun 2024

ASJC Scopus subject areas

Structural Biology
Molecular Biology

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10.1038/s41594-024-01251-4

Cite this

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abstract = "Gene expression is inherently noisy, posing a challenge to understanding how precise and reproducible patterns of gene expression emerge in mammals. Here we investigate this phenomenon using gastruloids, a three-dimensional in vitro model for early mammalian development. Our study reveals intrinsic reproducibility in the self-organization of gastruloids, encompassing growth dynamics and gene expression patterns. We observe a remarkable degree of control over gene expression along the main body axis, with pattern boundaries positioned with single-cell precision. Furthermore, as gastruloids grow, both their physical proportions and gene expression patterns scale proportionally with system size. Notably, these properties emerge spontaneously in self-organizing cell aggregates, distinct from many in vivo systems constrained by fixed boundary conditions. Our findings shed light on the intricacies of developmental precision, reproducibility and size scaling within a mammalian system, suggesting that these phenomena might constitute fundamental features of multicellularity.",

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AU - Merle, Mélody

AU - Friedman, Leah

AU - Chureau, Corinne

AU - Shoushtarizadeh, Armin

AU - Gregor, Thomas

N1 - Publisher Copyright: © The Author(s), under exclusive licence to Springer Nature America, Inc. 2024.

PY - 2024/6

Y1 - 2024/6

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Precise and scalable self-organization in mammalian pseudo-embryos

Abstract

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