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Systematically quantifying morphological features reveals constraints on organoid phenotypes

View ORCID ProfileLauren E. Beck, Jasmine Lee, Christopher Cote, Margaret C. Dunagin, Nikkita Salla, Marcello K. Chang, View ORCID ProfileAlex J. Hughes, Joseph D. Mornin, View ORCID ProfileZev J. Gartner, View ORCID ProfileArjun Raj
doi: https://doi.org/10.1101/2021.01.08.425947
Lauren E. Beck
1Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, USA
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Jasmine Lee
1Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, USA
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Christopher Cote
1Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, USA
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Margaret C. Dunagin
1Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, USA
2Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
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Nikkita Salla
1Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, USA
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Marcello K. Chang
1Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, USA
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Alex J. Hughes
1Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, USA
3Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
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Joseph D. Mornin
4Independent Researcher, Berkeley, CA, USA
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Zev J. Gartner
5Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA
6Center for Cellular Construction, University of California, San Francisco, San Francisco, CA, USA
7Chan Zuckerberg Biohub, San Francisco, CA, USA
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Arjun Raj
1Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, USA
2Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
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  • For correspondence: arjunrajlab@gmail.com
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Abstract

Organoids recapitulate complex 3D organ structures and represent a unique opportunity to probe the principles of self-organization. While we can alter an organoid’s morphology by manipulating the culture conditions, the morphology of an organoid often resembles that of its original organ, suggesting that organoid morphologies are governed by a set of tissue-specific constraints. Here, we establish a framework to identify constraints on an organoid’s morphological features by quantifying them from microscopy images of organoids exposed to a range of perturbations. We apply this framework to Madin-Darby Canine Kidney cysts and show that they obey a number of constraints taking the form of scaling relationships or caps on certain parameters. For example, we found that the number, but not size, of cells increases with increasing cyst size. We also find that these constraints vary with cyst age and can be altered by varying the culture conditions. This quantitative framework for identifying constraints on organoid morphologies may inform future efforts to engineer organoids.

Competing Interest Statement

AR receives royalties related to Stellaris RNA FISH probes. All other authors declare no competing interests.

Copyright 
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 January 08, 2021.
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Systematically quantifying morphological features reveals constraints on organoid phenotypes
Lauren E. Beck, Jasmine Lee, Christopher Cote, Margaret C. Dunagin, Nikkita Salla, Marcello K. Chang, Alex J. Hughes, Joseph D. Mornin, Zev J. Gartner, Arjun Raj
bioRxiv 2021.01.08.425947; doi: https://doi.org/10.1101/2021.01.08.425947
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Systematically quantifying morphological features reveals constraints on organoid phenotypes
Lauren E. Beck, Jasmine Lee, Christopher Cote, Margaret C. Dunagin, Nikkita Salla, Marcello K. Chang, Alex J. Hughes, Joseph D. Mornin, Zev J. Gartner, Arjun Raj
bioRxiv 2021.01.08.425947; doi: https://doi.org/10.1101/2021.01.08.425947

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