Human iPSC-derived hepatocyte system models cholestasis with tight junction protein 2 deficiency.

ABSTRACT:

Background & aims

The truncating mutations in tight junction protein 2 (TJP2) cause progressive cholestasis, liver failure, and hepatocyte carcinogenesis. Due to the lack of effective model systems, there are no targeted medications for the liver pathology with TJP2 deficiency. We leveraged the technologies of patient-specific induced pluripotent stem cells (iPSC) and CRISPR genome-editing, and we aim to establish a disease model which recapitulates phenotypes of patients with TJP2 deficiency.

Methods

We differentiated iPSC to hepatocyte-like cells (iHep) on the Transwell membrane in a polarized monolayer. Immunofluorescent staining of polarity markers was detected by a confocal microscope. The epithelial barrier function and bile acid transport of bile canaliculi were quant

SUBMITTER: Li CZ 

PROVIDER: S-EPMC8904612 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature