Institute of Epigenetics and Stem Cells (IES), Helmholtz Zentrum München, D-81377 München, Germany; email:
Institute of Functional Epigenetics (IFE) and Institute of Computational Biology (ICB), Helmholtz Zentrum München, D-85764 Neuherberg, Germany.
Annu Rev Genet. 2020 Nov 23;54:167-187. doi: 10.1146/annurev-genet-021920-110200. Epub 2020 Aug 31.
Cellular heterogeneity is a property of any living system; however, its relationship with cellular fate decision remains an open question. Recent technological advances have enabled valuable insights, especially in complex systems such as the mouse embryo. In this review, we discuss recent studies that characterize cellular heterogeneity at different levels during mouse development, from the two-cell stage up to gastrulation. In addition to key experimental findings, we review mathematical modeling approaches that help researchers interpret these findings. Disentangling the role of heterogeneity in cell fate decision will likely rely on the refined integration of experiments, large-scale omics data, and mathematical modeling, complemented by the use of synthetic embryos and gastruloids as promising in vitro models.
细胞异质性是任何生命系统的固有属性；然而，其与细胞命运决定的关系仍是一个悬而未决的问题。最近的技术进步为此提供了有价值的见解，尤其是在像小鼠胚胎这样的复杂系统中。在这篇综述中，我们讨论了最近的研究，这些研究描述了从小鼠胚胎的两细胞期到原肠胚形成阶段不同水平的细胞异质性。除了关键的实验发现，我们还回顾了有助于研究人员解释这些发现的数学建模方法。要想阐明异质性在细胞命运决定中的作用，可能需要将实验、大规模组学数据和数学建模进行精细化整合，同时辅之以使用合成胚胎和类原肠胚作为有前途的体外模型。
