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Inactivation of transcription factor HNF-1β with CRISPR/Cas9 induces epithelial-mesenchymal transition

ABSTRACT: Hepatocyte nuclear factor-1β (HNF-1β) is a tissue-specific transcription factor that is essential for the development of the kidney. Mutations of HNF-1β produce autosomal dominant tubulointerstitial kidney disease (ADTKD) characterized by tubular cysts, renal fibrosis, and progressive decline in kidney function. To understand the functions of HNF-1β, we generated HNF-1β-deficient mIMCD3 renal epithelial cells. Gene editing with CRISPR/Cas9 was used to delete exon 1 of HNF-1β by non-homologous end joining (NHEJ). We performed RNA-seq on three independent HNF-1β-deficient mIMCD3 cell lines and three paired control cell lines. Our RNA-seq of HNF-1β-deficient cells showed upregulation of 1,135 genes and repression of 759 genes compared to control cells. Pathway analysis revealed that fibrosis and epithelial-mesenchymal transition (EMT) pathways were highly activated in HNF-1β-deficient cells. We conclude that loss of HNF-1β in renal epithelial cells leads to the activation of a transcriptional network that induces EMT and aberrant TGFβ signaling. Targeting this network may inhibit fibrosis in ADTKD and other chronic kidney diseases.

ORGANISM(S): Mus musculus

PROVIDER: GSE97770 | GEO | 2018/08/10

REPOSITORIES: GEO

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Project description:Hnf-1β ChIP-Seq

| PRJNA290705 | ENA

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