PMID- 26365514 OWN - NLM STAT- MEDLINE DCOM- 20160802 LR - 20181113 IS - 2213-6711 (Electronic) IS - 2213-6711 (Linking) VI - 5 IP - 4 DP - 2015 Oct 13 TI - CPM Is a Useful Cell Surface Marker to Isolate Expandable Bi-Potential Liver Progenitor Cells Derived from Human iPS Cells. PG - 508-15 LID - S2213-6711(15)00242-8 [pii] LID - 10.1016/j.stemcr.2015.08.008 [doi] AB - 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. CI - Copyright (c) 2015 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Kido, Taketomo AU - Kido T AD - 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. FAU - Koui, Yuta AU - Koui Y AD - Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan. FAU - Suzuki, Kaori AU - Suzuki K AD - 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. FAU - Kobayashi, Ayaka AU - Kobayashi A AD - Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan. FAU - Miura, Yasushi AU - Miura Y AD - Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan. FAU - Chern, Edward Y AU - Chern EY AD - 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. FAU - Tanaka, Minoru AU - Tanaka M AD - Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan. FAU - Miyajima, Atsushi AU - Miyajima A AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150910 PL - United States TA - Stem Cell Reports JT - Stem cell reports JID - 101611300 RN - 0 (GPI-Linked Proteins) RN - EC 3.4.17.12 (carboxypeptidase M) RN - EC 3.4.24.- (Metalloendopeptidases) SB - IM MH - Animals MH - Cell Culture Techniques MH - Cell Differentiation MH - Cell Line MH - Cell Proliferation MH - Cell Separation MH - Cells, Cultured MH - Embryonic Stem Cells/cytology MH - GPI-Linked Proteins/analysis MH - Hepatocytes/*cytology MH - Humans MH - Induced Pluripotent Stem Cells/*cytology MH - Metalloendopeptidases/*analysis MH - Mice PMC - PMC4624956 EDAT- 2015/09/15 06:00 MHDA- 2016/08/03 06:00 PMCR- 2015/09/10 CRDT- 2015/09/15 06:00 PHST- 2015/04/08 00:00 [received] PHST- 2015/08/07 00:00 [revised] PHST- 2015/08/08 00:00 [accepted] PHST- 2015/09/15 06:00 [entrez] PHST- 2015/09/15 06:00 [pubmed] PHST- 2016/08/03 06:00 [medline] PHST- 2015/09/10 00:00 [pmc-release] AID - S2213-6711(15)00242-8 [pii] AID - 10.1016/j.stemcr.2015.08.008 [doi] PST - ppublish SO - Stem Cell Reports. 2015 Oct 13;5(4):508-15. doi: 10.1016/j.stemcr.2015.08.008. Epub 2015 Sep 10.