PT  - JOURNAL ARTICLE
AU  - Lauren E. Beck
AU  - Jasmine Lee
AU  - Christopher Cote
AU  - Margaret C. Dunagin
AU  - Nikkita Salla
AU  - Marcello K. Chang
AU  - Alex J. Hughes
AU  - Joseph D. Mornin
AU  - Zev J. Gartner
AU  - Arjun Raj
TI  - Systematically quantifying morphological features reveals constraints on organoid phenotypes
AID  - 10.1101/2021.01.08.425947
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.01.08.425947
4099  - http://biorxiv.org/content/early/2021/01/08/2021.01.08.425947.short
4100  - http://biorxiv.org/content/early/2021/01/08/2021.01.08.425947.full
AB  - 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 StatementAR receives royalties related to Stellaris RNA FISH probes. All other authors declare no competing interests.