RT Journal Article
SR Electronic
T1 Long-term live imaging of epithelial organoids and corresponding multiscale analysis reveal high heterogeneity and identify core regulatory principles
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.12.199463
DO 10.1101/2020.07.12.199463
A1 Lotta Hof
A1 Till Moreth
A1 Michael Koch
A1 Tim Liebisch
A1 Marina Kurtz
A1 Julia Tarnick
A1 Susanna M. Lissek
A1 Monique M.A. Verstegen
A1 Luc J.W. van der Laan
A1 Meritxell Huch
A1 Franziska Matthäus
A1 Ernst H.K. Stelzer
A1 Francesco Pampaloni
YR 2020
UL http://biorxiv.org/content/early/2020/07/16/2020.07.12.199463.abstract
AB Organoids are morphologically heterogeneous three-dimensional cell culture systems. To understand the cell organisation principles of their morphogenesis, we imaged hundreds of pancreas and liver organoids in parallel using light sheet and bright field microscopy for up to seven days. 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 macroscale analyses of entire cultures. Our multiscale analysis provides a systematic picture of the diversity of cell organisation in organoids by identifying and quantifying core regulatory principles of organoid morphogenesis.Graphical AbstractCreated with BioRender.com.Competing Interest StatementThe authors have declared no competing interest.