A human pluripotent stem cell-based somitogenesis model using microfluidics

Cell Stem Cell. 2024 Aug 1;31(8):1113-1126.e6. doi: 10.1016/j.stem.2024.06.004. Epub 2024 Jul 8.

Abstract

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.

Keywords: biomechanics; embryo model; human development; human pluripotent stem cells; in vitro modeling; microfluidics; somitogenesis.

MeSH terms

  • Cell Differentiation
  • Embryonic Development
  • Humans
  • Mesoderm / cytology
  • Microfluidics* / methods
  • Models, Biological*
  • Pluripotent Stem Cells* / cytology
  • Pluripotent Stem Cells* / metabolism
  • Somites* / cytology
  • Somites* / metabolism