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.

基因表达本质上是嘈杂的，这对理解哺乳动物中基因表达的精确性和可重复性模式如何出现提出了挑战。在这里，我们使用原肠胚来研究这种现象，这是一种早期哺乳动物发育的三维体外模型。我们的研究揭示了类原肠胚自组织的内在可重复性，包括生长动力学和基因表达模式。我们观察到沿主体轴的基因表达具有显着程度的控制，模式边界以单细胞精度定位。此外，随着原肠胚的生长，它们的物理比例和基因表达模式都与系统大小成正比。值得注意的是，这些特性在自组织细胞聚集体中自发出现，与许多受固定边界条件限制的体内系统不同。我们的发现揭示了哺乳动物系统内发育精度、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的基本特征。