Inflation-collapse dynamics drive patterning and morphogenesis in intestinal organoids

We apply single cell RNA-sequencing (scRNA-seq) to murine intestinal organoids in two experiments: 1) Comparing the transcriptomic landscape of organoids cultured in dome and sandwich culture systems (as described in the accompanying paper for this GEO submission), and 2) Assessing the transcriptomic landscape of organoids perturbed with CFTRinh-172 to inhibit inflation events, and with Forskolin to activate inflation events in the sandwich culture system, with respective controls. We find that the dome and sandwich culture systems produce similar abundance levels of each major specialized cell type, with similar marker gene expression shared across culture types. We find in the perturbation experiments a stretch-responsive cell state, similar in gene expression to several previously reported cell states, which is significantly more abundant in the Forskolin treated organoids compared to controls, and significantly less abundant in CFTRinh-172 treated organoids compared to controls. Additionally, we find that Stem and Enterocyte cell states are respectively, significantly less abundant, and more abundant in the Forskolin treated organoids compared to controls. Examination of transcriptomic landscapes of two murine intestinal organoid culture types: dome and sandwich culture systems; examination of transcriptomic landscape changes in murine intestinal organoids as a result of inflation perturbations.