Cell fate coordinates mechano-osmotic forces in intestinal crypt formation
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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.
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There are two main paths to overcome the use of non-specific ECM such as Matrigel: synthetic matrices with more complete control over composition and stiffness, and decellularized tissue to create tissue-specific matrices.
“There are two main paths to overcome the use of non-specific ECM such as Matrigel: one is the use of synthetic matrices with more complete control over composition and stiffness, and the other is to take decellularized tissue and create tissue-specific matrices205,243.”
From Organoids (2022) · cites this paper as [243]
The Materials and Methods (Light-sheet microscopy; Time course experiments of fixed organoid samples, pages unavailable) describe culturing organoids in Matrigel. Searches for synthetic matrices, control of composition or stiffness, and decellularized tissue found no passage discussing either proposed alternative to Matrigel. (LLM, conf=0.76)
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- Authors
- Yang, Q., Xue, S.-L., Chan, C. J., Rempfler, M., Vischi, D., Maurer-Gutierrez, F., Hiiragi, T., Hannezo, E., & Liberali, P.
- Affiliations
- Friedrich Miescher Institute (CH)
- Institute of Science and Technology Austria (AT)
- National University of Singapore (SG)
- European Molecular Biology Laboratory (DE)
- University of Basel (CH)
- Corresponding author
- Yang, Qiutan
- Liberali, Prisca
- Venue
- Nature Cell Biology
- Published
- 2021-06-21
- Volume
- 23
- Issue
- 7
- Pages
- 733-744
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- PMC
- PMC7611267
- OpenAlex
- W3175754720
- Cited by
- 183
- References
- 71
- Citations by year
- 2026: 21 · 2025: 33 · 2024: 25 · 2023: 36 · 2022: 45 · 2021: 19 · 2020: 4
- FWCI
- 16.32
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Nature Cell Biology (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- National University of Singapore (submittedVersion)
- Funders
- European Commission (HORIZON2020, 758617)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (157531)
- Austrian Science Fund (P31639)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- intestinal organoids, actomyosin contraction, cell swelling, sodium-glucose cotransporter, enterocytes, cell fate, morphogenesis, biophysical model, mechanical robustness
- MeSH terms
- Animals, Cell Differentiation, Cell Movement, Cells, Cultured, Computer Simulation, Female, Intestinal Mucosa, Male, Mice, Inbred C57BL, Mice, Transgenic, Models, Biological, Morphogenesis, Organoids, Osmotic Pressure, Stem Cells, Stress, Mechanical, Time Factors, Microscopy, Confocal, Microscopy, Video, Cell Lineage, Paneth Cells, Myosin Type II, Mechanotransduction, Cellular, Sodium-Glucose Transport Proteins, Mice, Osmoregulation
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