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

Stem Cell Research

Hiromi Chikada^1,2¹  Akihide Kamiya^1,2²  Kinuyo Ida^1³  Emi Ando^1⁴ 

[1] Center for Matrix Biology and Medicine, Graduate School of Medicine, Tokai University, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan^2;Department of Molecular Life Sciences, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, Japan^1;Department of Regenerative Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan^3;Division of Gastroenterology, Department of Internal Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan^4

关键词: Human iPS cells;    Polycystic liver disease;    Genome editing;    Cholangiocyte;   

DOI  :  10.1016/j.scr.2018.08.018

学科分类：生物科学（综合）

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Unknown