Cell fate coordinates mechano-osmotic forces in intestinal crypt formation

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.

Automated summary

This study reveals the simultaneous occurrence of crypt formation and reduction in lumen volume in intestinal organoids derived from single cells. By developing a 3D biophysical model and utilizing multiple mechanical perturbations, it demonstrates the synergistic effects of actomyosin-driven crypt apical contraction and villus basal tension with lumen volume reduction in driving crypt morphogenesis. Additionally, a sodium/glucose cotransporter specific to differentiated enterocytes was identified, which modulates lumen volume reduction through cell swelling in the villus region.