HNF1B Alters an Evolutionarily Conserved Nephrogenic Program of Target Genes.

ABSTRACT:

Significance statement

Mutations in hepatocyte nuclear factor-1 β ( HNF1B ) are the most common monogenic causes of congenital renal malformations. HNF1B is necessary to directly reprogram fibroblasts to induced renal tubule epithelial cells (iRECs) and, as we demonstrate, can induce ectopic pronephric tissue in Xenopus ectodermal organoids. Using these two systems, we analyzed the effect of HNF1B mutations found in patients with cystic dysplastic kidney disease. We found cross-species conserved targets of HNF1B, identified transcripts that are differentially regulated by the patient-specific mutant protein, and functionally validated novel HNF1B targets in vivo . These results highlight evolutionarily conserved transcriptional mechanisms and provide insights into the genetic circu

SUBMITTER: Grand K 

PROVIDER: S-EPMC10103355 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature