Multiomics analyses reveal the role of Glis3 in polycystic kidney disease
We performed unbiased transcriptional profiling and chromatin accessibility analyses on adult kidney tissues from allelic series of Pkd1 and Glis3 inactivation mouse models. Glis3 is a modifer of cyst progression whose inactivation exacerbates polycystic kidney disease. Through the integration of multiomic datasets, we generated hypotheses to explain the worsening phenotype observed in Pkd1 and Glis3 double mutants. Overall design: We performed RNA-Seq and ATAC-Seq on the same kidney tissues using the following genotypes: wild type, Glis3fl/fl; Pax8rtTA; TetOCre (Glis3KO), Pkd1fl/fl; Pax8rtTA; TetOCre (Pkd1KO), and Glis3fl/fl; Pkd1fl/fl; Pax8rtTA; TetOCre (Pkd1KO+Glis3KO). All mice received oral doxycycline from postnatal day 28 to 42 (P28-P42) and kidney tissues were harvested at P49 (7 weeks).