Long-term live imaging and multiscale analysis identify heterogeneity and core principles of epithelial organoid morphogenesis

  • 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 entire-culture (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.
Author:Lotta HofORCiD, Till Moreth, Michael Koch, Tim LiebischORCiD, Marina Kurtz, Julia Tarnick, Susanna M. LissekORCiD, Monique M. A. VerstegenORCiD, Luc J. W. van der LaanORCiD, Meritxell HuchORCiD, Franziska MatthäusORCiDGND, Ernst H. K. StelzerORCiDGND, Francesco PampaloniORCiDGND
Parent Title (English):BMC biology
Place of publication:Berlin ; Heidelberg
Document Type:Article
Date of Publication (online):2021/02/24
Date of first Publication:2021/02/24
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2023/01/31
Issue:art. 37
Article Number:37
Page Number:22
First Page:1
Last Page:22
Open Access funding enabled and organized by Projekt DEAL.
Wissenschaftliche Zentren und koordinierte Programme / Frankfurt Institute for Advanced Studies (FIAS)
Fachübergreifende Einrichtungen / Buchmann Institut für Molekulare Lebenswissenschaften (BMLS)
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0