TY  - JOUR
A1  - Hof, Lotta
A1  - Moreth, Till
A1  - Koch, Michael
A1  - Liebisch, Tim
A1  - Kurtz, Marina
A1  - Tarnick, Julia
A1  - Lissek, Susanna M.
A1  - Verstegen, Monique M. A.
A1  - Laan, Luc J. W. van der
A1  - Huch, Meritxell
A1  - Matthäus, Franziska
A1  - Stelzer, Ernst H. K.
A1  - Pampaloni, Francesco
T1  - Long-term live imaging and multiscale analysis identify heterogeneity and core principles of epithelial organoid morphogenesis
T2  - BMC biology
N2  - 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.
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62839
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-628399
SN  - 1741-7007
N1  - Open Access funding enabled and organized by Projekt DEAL.
VL  - 19
IS  - art. 37
SP  - 1
EP  - 22
PB  - Springer
CY  - Berlin ; Heidelberg
ER  -