Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10748545 | Biochemical and Biophysical Research Communications | 2016 | 6 Pages |
Abstract
The drug discovery research for cholestatic liver diseases has been hampered by the lack of a well-established human cholangiocyte model. Functional cholangiocyte-like cells differentiated from human induced pluripotent stem (iPS) cells are expected to be a promising candidate for such research, but there remains no well-established method for differentiating cholangiocytes from human iPS cells. In this study, we searched for a suitable extracellular matrix to promote cholangiocyte differentiation from human iPS cells, and found that both laminin 411 and laminin 511 were suitable for this purpose. The gene expression levels of the cholangiocyte markers, aquaporin 1 (AQP1), SRY-box 9 (SOX9), cystic fibrosis transmembrane conductance regulator (CFTR), G protein-coupled bile acid receptor 1 (GPBAR1), Jagged 1 (JAG1), secretin receptor (SCTR), and γ-glutamyl transferase (GGT1) were increased by using laminin 411 or laminin 511 as a matrix. In addition, the percentage of AQP1-positive cells was increased from 61.8% to 92.5% by using laminin 411 or laminin 511. Furthermore, the diameter and number of cysts consisted of cholangiocyte-like cells were increased when using either matrix. We believe that the human iPS cell-derived cholangiocyte-like cells, which were generated by using our differentiation technology, would be useful for the drug discovery research of cholestatic liver diseases.
Keywords
EGFSRY-box 9G protein-coupled bile acid receptor 1SCTRJAG1Jagged 1GPBAR1CholangiocyteAQP1HBCHGFIL6CFTRFGFSox9OSMFBSBSAiPSγ-Glutamyl transferasebovine serum albuminaquaporin 1oncostatin Minterleukin 6cystic fibrosis transmembrane conductance regulatorinduced pluripotent stemfetal bovine serumHuman induced pluripotent stem cellsepidermal growth factorHepatocyte growth factorfibroblast growth factorLamininBMPBone morphogenetic proteinSecretin receptor
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Authors
Kazuo Takayama, Seiji Mitani, Yasuhito Nagamoto, Fuminori Sakurai, Masashi Tachibana, Yukimasa Taniguchi, Kiyotoshi Sekiguchi, Hiroyuki Mizuguchi,