title: CPM Is a Useful Cell Surface Marker to Isolate Expandable Bi-Potential Liver Progenitor Cells Derived from Human iPS Cells.
abstract: To develop a culture system for large-scale production of mature hepatocytes, liver progenitor cells (LPCs) with a high proliferation potential would be advantageous. We have found that carboxypeptidase M (CPM) is highly expressed in embryonic LPCs, hepatoblasts, while its expression is decreased along with hepatic maturation. Consistently, CPM expression was transiently induced during hepatic specification from human-induced pluripotent stem cells (hiPSCs). CPM(+) cells isolated from differentiated hiPSCs at the immature hepatocyte stage proliferated extensively in vitro and expressed a set of genes that were typical of hepatoblasts. Moreover, the CPM(+) cells exhibited a mature hepatocyte phenotype after induction of hepatic maturation and also underwent cholangiocytic differentiation in a three-dimensional culture system. These results indicated that hiPSC-derived CPM(+) cells share the characteristics of LPCs, with the potential to proliferate and differentiate bi-directionally. Thus, CPM is a useful marker for isolating hiPSC-derived LPCs, which allows development of a large-scale culture system for producing hepatocytes and cholangiocytes.
authors.affiliation: Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan. Electronic address: kido@iam.u-tokyo.ac.jp.
authors.forename: Taketomo
authors.initials: T
authors.lastname: Kido
authors.affiliation: Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Koui
authors.affiliation: Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan; Department of Host Defense and Biochemical Research, Juntendo University, School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Kobayashi
authors.affiliation: Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Miura
authors.affiliation: Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan; Department of Biochemical Science and Technology, National Taiwan University, Taipei 106, Taiwan.
authors.forename: Edward Y
authors.initials: EY
authors.lastname: Chern
authors.affiliation: Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan. Electronic address: miyajima@iam.u-tokyo.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyajima
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology; D058851:GPI-Linked Proteins / Q000032:analysis; D022781:Hepatocytes / Q000166:cytology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D008666:Metalloendopeptidases / Q000032:analysis*; D051379:Mice
chemical_list: D058851:GPI-Linked Proteins; C058479:carboxypeptidase M; D008666:Metalloendopeptidases