A human pluripotent stem cell-based somitogenesis model using microfluidics

Emerging human pluripotent stem cell (hPSC)-based embryo models are useful for studying human embryogenesis. Particularly, there are hPSC-based somitogenesis models using free-floating culture that recapitulate somite formation. Somitogenesis in vivo involves intricately orchestrated biochemical and biomechanical events. However, none of the current somitogenesis models controls biochemical gradients or biomechanical signals in the culture, limiting their applicability to untangle complex biochemical-biomechanical interactions that drive somitogenesis. Herein, we develop a human somitogenesis model by confining hPSC-derived presomitic mesoderm (PSM) tissues in microfabricated trenches. Exogenous microfluidic morphogen gradients imposed on the PSM tissues cause axial patterning and trigger spontaneous rostral-to-caudal somite formation. A mechanical theory is developed to explain the size dependency between somites and the PSM. The microfluidic somitogenesis model is further exploited to reveal regulatory roles of cellular and tissue biomechanics in somite formation. This study presents a useful microengineered, hPSC-based model for understanding the biochemical and biomechanical events that guide somite formation. [Display omitted] •A spatially patterned somite development model in a microfluidic environment•Live imaging to track cellular and signaling dynamics during somite formation•A scaling law for somite size control is proposed based on a mechanical model•Somite development is dependent on various mechanical regulators Liu et al. develop a bioengineered somite development model with spatial patterning to study the cellular and signaling dynamics during somite formation. A mechanics-based scaling law underlying somite boundary formation is proposed, and the contributions of various mechanical regulators, such as intercellular adhesion, force generation, and mesenchymal-epithelial transition, are assessed.