Precise and scalable self-organization in mammalian pseudo-embryos

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.