摘要：SummaryMadin-Darby canine kidney II (MDCKII) cells are widely used to study epithelial morphogenesis. To better understand this process, we performed time course RNA-seq analysis of MDCKII 3D cystogenesis, along with polarized 2D cells for comparison. Our study reveals a biphasic change in the transcriptome that occurs after the first cell cycle and coincides with lumen establishment. This change appears to be linked to translocation of β-catenin, supported by analyses withAVL9- andDENND5A-knockdown clones, and regulation by HNF1B, supported by ATAC-seq study. These findings indicate a qualitative change model for transcriptome remodeling during epithelial morphogenesis, leading to cell proliferation decrease and cell polarity establishment. Furthermore, our study reveals that active mitochondria are retained and chromatin accessibility decreases in 3D cysts but not in 2D polarized cells. This indicates that 3D culture is a better model than 2D culture for studying epithelial morphogenesis.Graphical AbstractDisplay OmittedHighlights•The transcriptome switches after the first cell cycle and during MDCKII lumenogenesis•The transcriptome switch is linked to β-catenin translocation and HNF1B activation•Chromatin accessibility decreases during MDCKII cystogenesis•Active mitochondria are maintained in 3D, but not 2D, epithelial morphogenesisDevelopmental Biology; Embryology; Transcriptomics
