RNA-Seq of human pancreas organoids in expansion conditions in the presence of DMSO, CHIR99021 or CHIR99021 in the absence of FGF2

To investigate signaling pathways regulating human pancreas differentiation and morphogenesis, we developed a high-content image-based screen and quantitative multivariate analysis pipelines robust to heterogeneity to extract single-cell and organoid features using pancreatic progenitor organoids. Among the 54 hit compounds, we found that GSK3A/B inhibition via WNT signaling has a global reversible effect on cell identity, repressing pancreatic progenitor markers and inducing a poised state of progenitors transitioning to acinar cells. We show that additional FGF repression enables further differentiation of acinar cells recapitulating pancreatic acini morphogenesis and functions . This dataset compares human pancreas organoids produced from pluripotent stem cells by RNA-Seq in expansion conditions in the presence of DMSO (control) to those exposed for 7 days to CHIR99021 or CHIR99021 in the absence of the FGF2 normally included in the expansion medium.