An in vitro model of polycystic liver disease using genome-edited human inducible pluripotent stem cells

Stem Cell Research
Akihide KamiyaYutaka Inagaki

Abstract

In the developing liver, bile duct structure is formed through differentiation of hepatic progenitor cells (HPC) into cholangiocytes. A subtype of polycystic liver diseases characterized by uncontrolled expansion of bile ductal cells is caused by genetic abnormalities such as in that of protein kinase C substrate 80 K-H (PRKCSH). In this study, we aimed to mimic the disease process in vitro by genome editing of the PRKCSH locus in human inducible pluripotent stem (iPS) cells. A proportion of cultured human iPS cell-derived CD13+CD133+ HPC differentiated into CD13- cells. During the subsequent gel embedding culture, CD13- cells formed bile ductal marker-positive cystic structures with the polarity of epithelial cells. A deletion of PRKCSH gene increased expression of cholangiocytic transcription factors in CD13- cells and the number of cholangiocytic cyst structure. These results suggest that PRKCSH deficiency promotes the differentiation of HPC-derived cholangiocytes, providing a good in vitro model to analyze the molecular mechanisms underlying polycystic diseases.

Citations

Jan 29, 2019·Cardiovascular Research·Emily A PinheiroPaul W Burridge
Feb 23, 2020·Journal of Cardiovascular Translational Research·Emily A PinheiroPaul W Burridge
Sep 10, 2019·Immunological Medicine·Sei Kakinuma, Mamoru Watanabe

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