A Qualitative Change in the Transcriptome Occurs after the First Cell Cycle and Coincides with Lumen Establishment during MDCKII Cystogenesis

Tianfang Wang, Sang Ho Kwon, Xiao Peng, Severine Urdy, Zefu Lu, Robert J. Schmitz, Stephen Dalton, Keith E. Mostov, Shaying Zhao

Research output: Contribution to journalArticlepeer-review

Abstract

Madin-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 with AVL9- and DENND5A-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.

Original languageEnglish (US)
Article number101629
JournaliScience
Volume23
Issue number10
DOIs
StatePublished - Oct 23 2020

Keywords

  • Developmental Biology
  • Embryology
  • Transcriptomics

ASJC Scopus subject areas

  • General

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