@article{8b5727a21f6c4a4b86b41e25f20df26b,
title = "Generation of functional ciliated cholangiocytes from human pluripotent stem cells",
abstract = "The derivation of mature functional cholangiocytes from human pluripotent stem cells (hPSCs) provides a model for studying the pathogenesis of cholangiopathies and for developing therapies to treat them. Current differentiation protocols are not efficient and give rise to cholangiocytes that are not fully mature, limiting their therapeutic applications. Here, we generate functional hPSC-derived cholangiocytes that display many characteristics of mature bile duct cells including high levels of cystic fibrosis transmembrane conductance regulator (CFTR) and the presence of primary cilia capable of sensing flow. With this level of maturation, these cholangiocytes are amenable for testing the efficacy of cystic fibrosis drugs and for studying the role of cilia in cholangiocyte development and function. Transplantation studies show that the mature cholangiocytes generate ductal structures in the liver of immunocompromised mice indicating that it may be possible to develop cell-based therapies to restore bile duct function in patients with biliary disease.",
author = "Mina Ogawa and Jiang, {Jia Xin} and Sunny Xia and Donghe Yang and Avrilynn Ding and Onofrio Laselva and Marcela Hernandez and Changyi Cui and Yuichiro Higuchi and Hiroshi Suemizu and Craig Dorrell and Markus Grompe and Bear, {Christine E.} and Shinichiro Ogawa",
note = "Funding Information: We thank Dr. Michael Laflamme for providing GCaMP cell line, and Abbvie for providing the reference tool compounds AC1, AC2-1, AC2-2, and AP2. Dr. Sonya Mac-Parland, Dr. Gary Bader, and Dr. Ian McGilvray for providing the Counts Matrix data of primary human adult liver. We also thank Dr. Gordon Keller for his invaluable guidance and assistance. Induced pluripotent stem cells were obtained through the CF Canada-SickKids Program for Individualized CF Therapy (CFIT). The CFIT Program is jointly funded by the Sick Kids Foundation and Cystic Fibrosis Canada.This work is supported by the CFIT Program (C.E.B.), and JSPS KAKENHI grant number JP18K08589 (S.O.). This research is part of the Government of Canada through Genome Canada and the Ontario Genomics Institute (OGI-148) (awarded to C.E.B. and S.O.), and part of the University of Toronto{\textquoteright}s Medicine by Design initiative, funding from the Canada First Research Excellence fund (awarded to C.E.B. and S.O.). Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
doi = "10.1038/s41467-021-26764-0",
language = "English (US)",
volume = "12",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}