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Generation of functional ciliated cholangiocytes from human pluripotent stem cells
by
Yang, Donghe
, Ogawa, Mina
, Bear, Christine E.
, Jiang, Jia-Xin
, Cui, Changyi
, Xia, Sunny
, Ogawa, Shinichiro
, Grompe, Markus
, Hernandez, Marcela
, Suemizu, Hiroshi
, Laselva, Onofrio
, Dorrell, Craig
, Ding, Avrilynn
, Higuchi, Yuichiro
in
13
/ 13/100
/ 13/106
/ 13/51
/ 14/19
/ 14/28
/ 14/63
/ 38/47
/ 38/77
/ 45/90
/ 45/91
/ 631/136
/ 631/80
/ 692/699/1503/1328/1325
/ 82/1
/ Bile Duct Diseases - metabolism
/ Bile ducts
/ Cell Differentiation - physiology
/ Cilia
/ Cystic fibrosis
/ Cystic Fibrosis Transmembrane Conductance Regulator - metabolism
/ Developmental Biology
/ Drug development
/ Epithelial Cells - cytology
/ Epithelial Cells - metabolism
/ Humanities and Social Sciences
/ Humans
/ Immunosuppressive agents
/ In vivo methods and tests
/ Induced Pluripotent Stem Cells - cytology
/ Induced Pluripotent Stem Cells - metabolism
/ Kinases
/ Maturation
/ multidisciplinary
/ Pathogenesis
/ Pluripotency
/ Pluripotent Stem Cells - cytology
/ Pluripotent Stem Cells - metabolism
/ Recovery of function
/ Retinoic acid
/ Rho-associated kinase
/ Science
/ Science (multidisciplinary)
/ Stem cell transplantation
/ Stem cells
/ Therapeutic applications
/ Transplantation
2021
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Generation of functional ciliated cholangiocytes from human pluripotent stem cells
by
Yang, Donghe
, Ogawa, Mina
, Bear, Christine E.
, Jiang, Jia-Xin
, Cui, Changyi
, Xia, Sunny
, Ogawa, Shinichiro
, Grompe, Markus
, Hernandez, Marcela
, Suemizu, Hiroshi
, Laselva, Onofrio
, Dorrell, Craig
, Ding, Avrilynn
, Higuchi, Yuichiro
in
13
/ 13/100
/ 13/106
/ 13/51
/ 14/19
/ 14/28
/ 14/63
/ 38/47
/ 38/77
/ 45/90
/ 45/91
/ 631/136
/ 631/80
/ 692/699/1503/1328/1325
/ 82/1
/ Bile Duct Diseases - metabolism
/ Bile ducts
/ Cell Differentiation - physiology
/ Cilia
/ Cystic fibrosis
/ Cystic Fibrosis Transmembrane Conductance Regulator - metabolism
/ Developmental Biology
/ Drug development
/ Epithelial Cells - cytology
/ Epithelial Cells - metabolism
/ Humanities and Social Sciences
/ Humans
/ Immunosuppressive agents
/ In vivo methods and tests
/ Induced Pluripotent Stem Cells - cytology
/ Induced Pluripotent Stem Cells - metabolism
/ Kinases
/ Maturation
/ multidisciplinary
/ Pathogenesis
/ Pluripotency
/ Pluripotent Stem Cells - cytology
/ Pluripotent Stem Cells - metabolism
/ Recovery of function
/ Retinoic acid
/ Rho-associated kinase
/ Science
/ Science (multidisciplinary)
/ Stem cell transplantation
/ Stem cells
/ Therapeutic applications
/ Transplantation
2021
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Generation of functional ciliated cholangiocytes from human pluripotent stem cells
by
Yang, Donghe
, Ogawa, Mina
, Bear, Christine E.
, Jiang, Jia-Xin
, Cui, Changyi
, Xia, Sunny
, Ogawa, Shinichiro
, Grompe, Markus
, Hernandez, Marcela
, Suemizu, Hiroshi
, Laselva, Onofrio
, Dorrell, Craig
, Ding, Avrilynn
, Higuchi, Yuichiro
in
13
/ 13/100
/ 13/106
/ 13/51
/ 14/19
/ 14/28
/ 14/63
/ 38/47
/ 38/77
/ 45/90
/ 45/91
/ 631/136
/ 631/80
/ 692/699/1503/1328/1325
/ 82/1
/ Bile Duct Diseases - metabolism
/ Bile ducts
/ Cell Differentiation - physiology
/ Cilia
/ Cystic fibrosis
/ Cystic Fibrosis Transmembrane Conductance Regulator - metabolism
/ Developmental Biology
/ Drug development
/ Epithelial Cells - cytology
/ Epithelial Cells - metabolism
/ Humanities and Social Sciences
/ Humans
/ Immunosuppressive agents
/ In vivo methods and tests
/ Induced Pluripotent Stem Cells - cytology
/ Induced Pluripotent Stem Cells - metabolism
/ Kinases
/ Maturation
/ multidisciplinary
/ Pathogenesis
/ Pluripotency
/ Pluripotent Stem Cells - cytology
/ Pluripotent Stem Cells - metabolism
/ Recovery of function
/ Retinoic acid
/ Rho-associated kinase
/ Science
/ Science (multidisciplinary)
/ Stem cell transplantation
/ Stem cells
/ Therapeutic applications
/ Transplantation
2021
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Generation of functional ciliated cholangiocytes from human pluripotent stem cells
Journal Article
Generation of functional ciliated cholangiocytes from human pluripotent stem cells
2021
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Overview
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.
Current protocols to generate cholangiocytes from human pluripotent cells produce immature cells. Here the authors identify retinoic acid, BMP, cAMP and Rho kinase pathways as regulators of cholangiocyte maturation, and generate ciliated cholangiocytes expressing high levels of CFTR that form ductal structures in vivo.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/100
/ 13/106
/ 13/51
/ 14/19
/ 14/28
/ 14/63
/ 38/47
/ 38/77
/ 45/90
/ 45/91
/ 631/136
/ 631/80
/ 82/1
/ Bile Duct Diseases - metabolism
/ Cell Differentiation - physiology
/ Cilia
/ Cystic Fibrosis Transmembrane Conductance Regulator - metabolism
/ Epithelial Cells - metabolism
/ Humanities and Social Sciences
/ Humans
/ Induced Pluripotent Stem Cells - cytology
/ Induced Pluripotent Stem Cells - metabolism
/ Kinases
/ Pluripotent Stem Cells - cytology
/ Pluripotent Stem Cells - metabolism
/ Science
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