Loss of LPAR6 and CAB39L Dysregulate Basal to Luminal Urothelial Differentiation Program Contributing to Bladder Carcinogenesis

In vitro and in vivo studies including single cell sequencing showed that LPAR6 and CAB39L play a major role in regulating basal to luminal urothelial differentiation. Their loss of function contributed to bladder carcinogenesis by dysregulating urothelial differentiation program and sensitizing the urothelium to N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) induced cancers, which recapitulated luminal and basal subtypes of human bladder cancer. Overall design: Single cell sequencing of the bladder urothelium was performed on cells harvested from wild type, Lpar6 knockout and Cab39l knockout mice. For each group a pooled sample of single urothelial cell suspension harvested from 15 mice was prepared.