Cell fate coordinates mechano-osmotic forces in intestinal crypt formation
Autor: | Qiutan Yang, Markus Rempfler, Prisca Liberali, Francisca Maurer-Gutierrez, Chii J. Chan, Takashi Hiiragi, Dario Vischi, Shi-Lei Xue, Edouard Hannezo |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Male
Paneth Cells Time Factors Contraction (grammar) Cell Crypt Morphogenesis Mice Transgenic Cell fate determination Mechanotransduction Cellular Models Biological Sodium-Glucose Transport Proteins digestive system Article 03 medical and health sciences Osmoregulation 0302 clinical medicine Cell Movement Osmotic Pressure medicine Animals Cell Lineage Computer Simulation Intestinal Mucosa Cells Cultured 030304 developmental biology Myosin Type II 0303 health sciences Lumen volume Microscopy Confocal Microscopy Video Chemistry Stem Cells digestive oral and skin physiology Cell Differentiation Cell Biology Cell biology Mice Inbred C57BL Organoids medicine.anatomical_structure 030220 oncology & carcinogenesis Female Stress Mechanical Stem cell Cotransporter |
Zdroj: | Nature cell biology Nature Cell Biology BASE-Bielefeld Academic Search Engine |
ISSN: | 1476-4679 1465-7392 |
Popis: | 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. Yang, Xue et al. demonstrate in intestinal organoids that region-specific cell fates drive actomyosin patterns and modulate luminal osmotic forces to coordinate morphogenesis. |
Databáze: | OpenAIRE |
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