Elucidating the Proximal Tubule HNF4A Gene Regulatory Network in Human Kidney Organoids.

ABSTRACT:

Significance statement

HNF4 genes promote proximal tubule differentiation in mice, but their function in human nephrogenesis is not fully defined. This study uses human pluripotent stem cell (PSC)-derived kidney organoids as a model to investigate HNF4A and HNF4G functions. The loss of HNF4A , but not HNF4G , impaired reabsorption-related molecule expression and microvilli formation in human proximal tubules. Cleavage under targets and release using nuclease (CUT&RUN) sequencing and CRISPR-mediated transcriptional activation (CRISPRa) further confirm that HNF4A directly regulates its target genes. Human kidney organoids provide a good model for studying transcriptional regulation in human kidney development.

Background

The proximal tubule plays a major role in electrolyte ho

SUBMITTER: Yoshimura Y 

PROVIDER: S-EPMC10561821 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature