The emergence of human gastrulation uponin vitroattachment

Abstract

AbstractWhile studied extensively in model systems, human gastrulation remains obscure. This process starts upon blastocyst implantation into the uterine wall, which is assumed to occur after 14 days post-fertilization. The scarcity and limited access to fetal biological material as well as ethical considerations limit our understanding of the cellular and molecular portrait of human gastrulation.In vitroculture of natural human blastocysts shed light on the second week of human development, unveiling an unexpected level of self-organization embedded in the pre-gastrulating embryo, yet whether they can undergo gastrulation uponin vitroattachment remains elusive. Blastocyst models calledblastoids, which are derived from human pluripotent stem cells, provide the opportunity to reconstitute post-implantation human developmentin vitrowith unlimited biological material. Here we show that humanblastoidsbreak symmetry and undergo gastrulation uponin vitroattachment. scRNA-seq of these models replicate the transcriptomic signature of the natural human gastrula, recapitulating aspects of the second to the third week of human development. Surprisingly, analysis of developmental timing reveals that in bothblastoidmodels and naturalin vitroattached human embryos, the onset of gastrulation as defined by molecular makers, can be traced to time scales equivalent to 12 days post-fertilization, which appeals for a reconsideration of the onset of human gastrulation upon extendedin vitroculture.