1. Cell fate coordinates mechano-osmotic forces in intestinal crypt formation.
- Author
-
Yang Q, Xue SL, Chan CJ, Rempfler M, Vischi D, Maurer-Gutierrez F, Hiiragi T, Hannezo E, and Liberali P
- Subjects
- Animals, Cell Movement, Cells, Cultured, Computer Simulation, Female, Intestinal Mucosa cytology, Intestinal Mucosa metabolism, Male, Mice, Inbred C57BL, Mice, Transgenic, Microscopy, Confocal, Microscopy, Video, Models, Biological, Morphogenesis, Myosin Type II genetics, Myosin Type II metabolism, Organoids, Osmotic Pressure, Paneth Cells metabolism, Sodium-Glucose Transport Proteins genetics, Sodium-Glucose Transport Proteins metabolism, Stem Cells metabolism, Stress, Mechanical, Time Factors, Mice, Cell Differentiation, Cell Lineage, Intestinal Mucosa physiology, Mechanotransduction, Cellular, Osmoregulation, Paneth Cells physiology, Stem Cells physiology
- Abstract
Intestinal organoids derived from single cells undergo complex crypt-villus patterning and morphogenesis. However, the nature and coordination of the underlying forces remains poorly characterized. Here, using light-sheet microscopy and large-scale imaging quantification, we demonstrate that crypt formation coincides with a stark reduction in lumen volume. We develop a 3D biophysical model to computationally screen different mechanical scenarios of crypt morphogenesis. Combining this with live-imaging data and multiple mechanical perturbations, we show that actomyosin-driven crypt apical contraction and villus basal tension work synergistically with lumen volume reduction to drive crypt morphogenesis, and demonstrate the existence of a critical point in differential tensions above which crypt morphology becomes robust to volume changes. Finally, we identified a sodium/glucose cotransporter that is specific to differentiated enterocytes that modulates lumen volume reduction through cell swelling in the villus region. Together, our study uncovers the cellular basis of how cell fate modulates osmotic and actomyosin forces to coordinate robust morphogenesis., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2021
- Full Text
- View/download PDF