A microwell platform for high-throughput longitudinal phenotyping and selective retrieval of organoids

• DOI: 10.1101/2022.11.01.514733
• Publication Date: 2022-11-03T03:25:13Z
• Authors: Alexandra Sockell; Wing Wong; Scott Longwell; Thy Vu; Kasper Karlsson; Daniel Mokhtari; Julia Schaepe; Yuan-Hung Lo; Vincent Cornelius; Calvin Kuo; David Van Valen; Christina Curtis; Polly M. Fordyce
• Keywords: Organoid; Polarity (international relations)

Summary Organoids are powerful experimental models for studying the ontogeny and progression of diseases including cancer. conventionally cultured in bulk using an extracellular matrix mimic. However, organoids culture physically overlap, making it impossible to track growth individual over time high throughput. Moreover, local spatial variations properties make difficult assess whether observed phenotypic heterogeneity between results from intrinsic cell differences or microenvironment variability. Here, we developed a microwell-based method that enables high-throughput quantification image-based parameters grown single cells, which can be retrieved their microwells sequencing molecular profiling. Coupled with deep-learning image processing pipeline, characterized traits rates, cellular movement, apical-basal polarity two CRISPR-engineered human gastric organoid models, identifying genomic changes associated increased rate accessibility expression correlated polarity.