The DOI matches its Crossref record; 71 of the 71 references it cites were found in a registry or an index.
Cell fate coordinates mechano-osmotic forces in intestinal crypt formation
Open accessPublished version of a preprint
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: 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]
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Cites
Going deeper with convolutions
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Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche
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A global double-fluorescent Cre reporter mouse
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Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts
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Growing Self-Organizing Mini-Guts from a Single Intestinal Stem Cell: Mechanism and Applications
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Chemical activation of the mechanotransduction channel Piezo1
Syeda, R., Xu, J., Dubin, A. E., Coste, B., Mathur, J., Huynh, T. T., Matzen, J., Lao, J., Tully, D. C., Engels, I. H., et al. (2015) · eLife · doi:10.7554/elife.07369 · Cited by 747
Myosin II Dynamics Are Regulated by Tension in Intercalating Cells
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Self-organization and symmetry breaking in intestinal organoid development
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Zhao, Z., Chen, X., Dowbaj, A. M., Sljukic, A., Bratlie, K., Lin, L., Fong, E. L. S., Balachander, G. M., Chen, Z., Soragni, A., et al. (2022) · Nature Reviews Methods Primers · doi:10.1038/s43586-022-00174-y · Cited by 1,082
“Part f adapted from ref.(243), Springer Nature Limited.”
BackgroundSynthetic dynamic hydrogels promote degradation-independent in vitro organogenesis
Chrisnandy, A., Blondel, D., Rezakhani, S., Broguiere, N., & Lutolf, M. P. (2022) · Nature Materials · doi:10.1038/s41563-021-01136-7 · Cited by 237
Pérez-González, C., Ceada, G., Greco, F., Matejčić, M., Gómez-González, M., Castro, N., Menendez, A., Kale, S., Krndija, D., Clark, A. G., et al. (2021) · Nature Cell Biology · doi:10.1038/s41556-021-00699-6 · Cited by 225
Curvature in Biological Systems: Its Quantification, Emergence, and Implications across the Scales
Schamberger, B., Ziege, R., Anselme, K., Amar, M. B., Bykowski, M., Castro, A. P. G., Cipitria, A., Coles, R., Dimova, R., Eder, M., et al. (2022) · Advanced Materials · doi:10.1002/adma.202206110 · Cited by 174
Adherens junctions as molecular regulators of emergent tissue mechanics
Campàs, O., Noordstra, I., & Yap, A. S. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00688-7 · Cited by 149
Metadata
- 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
- 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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