Synthetic Human Organogenesis: In Vitro Reconstitution and Mechanical Models of Human Somitogenesis

Somite is a unique structure of early-stage vertebrate embryo, which later becomes our musculoskeletal system. It acquires a segmented morphology (just like our vertebrae) through a sequence of boundary formation dynamics on a continuous strip of cells called pre-somitic mesoderm. This segmented morphology also defines the discontinuous topology of our bones and muscles, which are separated by joints and interfaces and therefore facilitate mechanical flexibility. However, a variety of fundamental questions regarding the somites remain unanswered due the our lack of understanding towards the morphogenetic driving forces. For example, different vertebrate species can have significantly different number of somites (e.g. ~40 pairs in human and ~315 in corn snake) and hence vertebrae, yet little is known about the underlying mechanism. To address this challenge, we combined human pluripotent stem cells and microfluidic tools and successfully induced an in vitro spatially directed somite boundary formation dynamics. Further, we established a mechanics-based theoretical scaling law to predict the somite size, which is confirmed by both in vivo and in vitro data from multiple species. Based on this work, we will be able to further probe the mechanical and biological principles dictating the somite formation process, and fully unveil the topology regulation mechanism of our musculoskeletal system.