The Transcription Factor Foxi1 Promotes Expression of V-ATPase and Gpr116 in M-1 cells

Abstract

AbstractThe diverse functions of each nephron segment rely on the coordinated action of specialized cell populations that are uniquely defined by their transcriptional profile. In the collecting duct, there are two critical and distinct cell populations: principal cells and intercalated cells. Principal cells play key roles in the regulation of water, Na+, and K+, while intercalated cells are best known for their role in acid-base homeostasis. Currently, there are noin vitrosystems that recapitulate the heterogeneity of the collecting ducts, which limits high-throughput and replicate investigations of genetic and physiological phenomena. Here, we have demonstrated that the transcription factor Foxi1 is sufficient to alter the transcriptional identity of M-1 cells, a murine cortical collecting duct cell line. Specifically, overexpression ofFoxi1induces the expression of intercalated cell transcripts includingGpr116, Atp6v1b1, Atp6v1g3, Atp6v0d2, Slc4a9, andSlc26a4. These data indicate that overexpression ofFoxi1differentiates M-1 cells towards a B-type intercalated cell phenotype and may provide a novelin vitrotool to study transcriptional regulation and physiological function of the renal collecting duct.