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A human pluripotent stem cell-based somitogenesis model microfluidics
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DOI：10.1016/j.stem.2024.06.004.png)
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Abstract
En 中文
Emerging human pluripotent stem cell (hPSC)-based embryo models are useful for studying human embryo- genesis. 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 rostralto-caudal somite formation. A mechanical theory is developed to explain the size dependency between so- mites 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:
TO-EPITHELIAL TRANSITION
HUMAN SEGMENTATION CLOCK
SELF-ORGANIZATION
SYMMETRY-BREAKING
SOMITE BOUNDARY
GENE
ELONGATION
PARAXIS
NUMBER
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