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Title: Differentiation and isolation of iPSC-derived remodeling ductal plate-like cells by use of an AQP1-GFP reporter human iPSC line
Authors: Matsui, Satoshi
Ochiai, Miyuki
Yasuda, Katsutaro
Mae, Shin ichi
Kotaka, Maki
Toyoda, Taro  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-2948-0525 (unconfirmed)
Yamamoto, Takuya  kyouindb  KAKEN_id
Osafune, Kenji  kyouindb  KAKEN_id
Author's alias: 落合, 美由希
安田, 勝太郎
前, 伸一
小髙, 真希
豊田, 太郎
山本, 拓也
長船, 健二
Keywords: iPSC
Differentiation
Cholangiocyte progenitor
Remodeling ductal plate cell
IsolationAQP1
Issue Date: Mar-2019
Publisher: Elsevier B.V.
Journal title: Stem Cell Research
Volume: 35
Thesis number: 101400
Abstract: Cholangiocytes are the epithelial cells that line bile ducts, and ductal plate malformation is a developmental anomaly of bile ducts that causes severe congenital biliary disorders. However, because of a lack of specific marker genes, methods for the stepwise differentiation and isolation of human induced pluripotent stem cell (hiPSC)-derived cholangiocyte progenitors at ductal plate stages have not been established. We herein generated an AQP1-GFP reporter hiPSC line and developed a combination treatment with transforming growth factor (TGF) β2 and epidermal growth factor (EGF) to induce hiPSC-derived hepatoblasts into AQP1⁺ cells in vitro. By confirming that the isolated AQP1⁺ cells showed similar gene expression patterns to cholangiocyte progenitors at the remodeling ductal plate stage around gestational week (GW) 20, we established a differentiation protocol from hiPSCs through SOX9⁺CK19⁺AQP1⁺ remodeling ductal plate-like cells. We further generated 3D bile duct-like structures from the induced ductal plate-like cells. These results suggest that AQP1 is a useful marker for the generation of remodeling ductal plate cells from hiPSCs. Our methods may contribute to elucidating the differentiation mechanisms of ductal plate cells and the pathogenesis of ductal plate malformation.
Rights: © 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/BY/4.0/).
URI: http://hdl.handle.net/2433/236393
DOI(Published Version): 10.1016/j.scr.2019.101400
PubMed ID: 30735882
Appears in Collections:Journal Articles

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