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哺乳动物类胚胎中的精确可扩展的自我组织。

Precise and scalable self-organization in mammalian pseudo-embryos.

机构信息

Department of Developmental and Stem Cell Biology, CNRS UMR3738 Paris Cité, Institut Pasteur, Paris, France.

Joseph Henry Laboratories of Physics & Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.

出版信息

Nat Struct Mol Biol. 2024 Jun;31(6):896-902. doi: 10.1038/s41594-024-01251-4. Epub 2024 Mar 15.

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.

摘要

基因表达本质上是嘈杂的,这给理解哺乳动物中精确和可重复的基因表达模式是如何出现的带来了挑战。在这里,我们使用原肠胚,一种用于早期哺乳动物发育的三维体外模型来研究这一现象。我们的研究揭示了原肠胚自我组织中的内在可重复性,包括生长动态和基因表达模式。我们观察到对沿主体轴的基因表达的显著控制程度,图案边界以单细胞精度定位。此外,随着原肠胚的生长,其物理比例和基因表达模式与系统大小成比例地缩放。值得注意的是,这些特性是在自我组织的细胞聚集体中自发出现的,与许多受固定边界条件限制的体内系统不同。我们的研究结果揭示了哺乳动物系统中发育精确性、可重复性和尺寸缩放的复杂性,表明这些现象可能构成多细胞性的基本特征。

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