biostudies-literatureSanman LENIBIB NIH HHSNIDDK NIH HHSNCI NIH HHSNational Institutes of HealthNIGMS NIH HHSNational Science Foundation356-365.e9https://www.ebi.ac.uk/biostudies/studies/S-EPMC7917018biostudies-literatureUnknown56(3)Renewing tissues have the remarkable ability to continually produce both proliferative progenitor and specialized differentiated cell types. How are complex milieus of microenvironmental signals interpreted to coordinate tissue-cell-type composition? Here, we investigate the responses of intestinal epithelium to individual and paired perturbations across eight epithelial signaling pathways. Using a high-throughput approach that combines enteroid monolayers and quantitative imaging, we identified conditions that enrich for specific cell types as well as interactions between pathways. Importantly, we found that modulation of transit-amplifying cell proliferation changes the ratio of differentiated secretory to absorptive cell types. These observations highlight an underappreciated role for tDevelopmental cellTransit-Amplifying Cells Coordinate Changes in Intestinal Epithelial Cell-Type Composition.PMC7917018R01 CA184984R01 GM112690F32 DK120102T32 EB009383R01 DK126376Trentesaux CKlein ODBieber JMWu LFSanman LEAltschuler SJChen IWHann BSteri VfalseTransit-Amplifying Cells Coordinate Changes in Intestinal Epithelial Cell-Type Composition.Renewing tissues have the remarkable ability to continually produce both proliferative progenitor and specialized differentiated cell types. How are complex milieus of microenvironmental signals interpreted to coordinate tissue-cell-type composition? Here, we investigate the responses of intestinal epithelium to individual and paired perturbations across eight epithelial signaling pathways. Using a high-throughput approach that combines enteroid monolayers and quantitative imaging, we identified conditions that enrich for specific cell types as well as interactions between pathways. Importantly, we found that modulation of transit-amplifying cell proliferation changes the ratio of differentiated secretory to absorptive cell types. These observations highlight an underappreciated role for t2021-01-01T00:00:00Z2021 Feb2025-04-18T15:12:48.2Z2025-04-07T01:45:56.087ZS-EPMC79170183348464010.1016/j.devcel.2020.12.020