Hof, Lotta and Moreth, Till and Koch, Michael and Liebisch, Tim and Kurtz, Marina and Tarnick, Julia and Lissek, Susanna M. and Verstegen, Monique M. A. and van der Laan, Luc J. W. and Huch, Meritxell and Matthaeus, Franziska and Stelzer, Ernst H. K. and Pampaloni, Francesco (2021) Long-term live imaging and multiscale analysis identify heterogeneity and core principles of epithelial organoid morphogenesis. BMC BIOLOGY, 19 (1): 37. ISSN , 1741-7007
Full text not available from this repository. (Request a copy)Abstract
Background: Organoids are morphologically heterogeneous three-dimensional cell culture systems and serve as an ideal model for understanding the principles of collective cell behaviour in mammalian organs during development, homeostasis, regeneration, and pathogenesis. To investigate the underlying cell organisation principles of organoids, we imaged hundreds of pancreas and cholangiocarcinoma organoids in parallel using light sheet and bright-field microscopy for up to 7 days. Results: We quantified organoid behaviour at single-cell (microscale), individual-organoid (mesoscale), and entireculture (macroscale) levels. At single-cell resolution, we monitored formation, monolayer polarisation, and degeneration and identified diverse behaviours, including lumen expansion and decline (size oscillation), migration, rotation, and multi-organoid fusion. Detailed individual organoid quantifications lead to a mechanical 3D agent-based model. A derived scaling law and simulations support the hypotheses that size oscillations depend on organoid properties and cell division dynamics, which is confirmed by bright-field microscopy analysis of entire cultures. Conclusion: Our multiscale analysis provides a systematic picture of the diversity of cell organisation in organoids by identifying and quantifying the core regulatory principles of organoid morphogenesis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MODELING DEVELOPMENT; SELF-ORGANIZATION; LUMEN; DISEASE; ESTABLISHMENT; EXPANSION; JUNCTIONS; CULTURE; FUSION; MOTION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für experimentelle Medizin und Therapieverfahren |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Sep 2022 14:07 |
| Last Modified: | 20 Sep 2022 14:07 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47739 |
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