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Long-term live imaging of epithelial organoids and corresponding multiscale analysis reveal high heterogeneity and identify core regulatory principles

Lotta Hof, Till Moreth, Michael Koch, Tim Liebisch, Marina Kurtz, Julia Tarnick, Susanna M. Lissek, Monique M.A. Verstegen, Luc J.W. van der Laan, Meritxell Huch, Franziska Matthäus, Ernst H.K. Stelzer, View ORCID ProfileFrancesco Pampaloni
doi: https://doi.org/10.1101/2020.07.12.199463
Lotta Hof
1Physical Biology Group, Buchmann Institute for Molecular Life Sciences (BMLS), Goethe-Universität Frankfurt am Main, Frankfurt am Main, Germany
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Till Moreth
1Physical Biology Group, Buchmann Institute for Molecular Life Sciences (BMLS), Goethe-Universität Frankfurt am Main, Frankfurt am Main, Germany
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Michael Koch
1Physical Biology Group, Buchmann Institute for Molecular Life Sciences (BMLS), Goethe-Universität Frankfurt am Main, Frankfurt am Main, Germany
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Tim Liebisch
2Faculty of Biological Sciences & Frankfurt Institute for Advanced Studies (FIAS), Goethe-Universität Frankfurt am Main, Frankfurt am Main, Germany
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Marina Kurtz
3Department of Physics & Frankfurt Institute for Advanced Studies (FIAS), Goethe-Universität Frankfurt am Main, Frankfurt am Main, Germany
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Julia Tarnick
4Deanery of Biomedical Science, University of Edinburgh, Edinburgh, United Kingdom
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Susanna M. Lissek
5Experimental Medicine and Therapy Research, University of Regensburg, Regensburg, Germany
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Monique M.A. Verstegen
6Department of Surgery, Erasmus MC – University Medical Center, Rotterdam, The Netherlands
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Luc J.W. van der Laan
6Department of Surgery, Erasmus MC – University Medical Center, Rotterdam, The Netherlands
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Meritxell Huch
7The Wellcome Trust/CRUK Gurdon Institute, University of Cambridge, Cambridge, United Kingdom
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Franziska Matthäus
2Faculty of Biological Sciences & Frankfurt Institute for Advanced Studies (FIAS), Goethe-Universität Frankfurt am Main, Frankfurt am Main, Germany
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Ernst H.K. Stelzer
1Physical Biology Group, Buchmann Institute for Molecular Life Sciences (BMLS), Goethe-Universität Frankfurt am Main, Frankfurt am Main, Germany
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Francesco Pampaloni
1Physical Biology Group, Buchmann Institute for Molecular Life Sciences (BMLS), Goethe-Universität Frankfurt am Main, Frankfurt am Main, Germany
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  • ORCID record for Francesco Pampaloni
  • For correspondence: f.pampalo@bio.uni-frankfurt.de
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Abstract

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.

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Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Typos in the title and in the affiliations have been corrected.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted July 16, 2020.
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Long-term live imaging of epithelial organoids and corresponding multiscale analysis reveal high heterogeneity and identify core regulatory principles
Lotta Hof, Till Moreth, Michael Koch, Tim Liebisch, Marina Kurtz, Julia Tarnick, Susanna M. Lissek, Monique M.A. Verstegen, Luc J.W. van der Laan, Meritxell Huch, Franziska Matthäus, Ernst H.K. Stelzer, Francesco Pampaloni
bioRxiv 2020.07.12.199463; doi: https://doi.org/10.1101/2020.07.12.199463
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Long-term live imaging of epithelial organoids and corresponding multiscale analysis reveal high heterogeneity and identify core regulatory principles
Lotta Hof, Till Moreth, Michael Koch, Tim Liebisch, Marina Kurtz, Julia Tarnick, Susanna M. Lissek, Monique M.A. Verstegen, Luc J.W. van der Laan, Meritxell Huch, Franziska Matthäus, Ernst H.K. Stelzer, Francesco Pampaloni
bioRxiv 2020.07.12.199463; doi: https://doi.org/10.1101/2020.07.12.199463

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