CPM Is a Useful Cell Surface Marker to Isolate Expandable Bi-Potential Liver Progenitor Cells Derived from Human iPS Cells

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 al...

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Published in:	Stem cell reports Vol. 5; no. 4; pp. 508 - 515
Main Authors:	Kido, Taketomo, Koui, Yuta, Suzuki, Kaori, Kobayashi, Ayaka, Miura, Yasushi, Chern, Edward Y., Tanaka, Minoru, Miyajima, Atsushi
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 13-10-2015 Elsevier
Subjects:	Animals Cell Culture Techniques Cell Differentiation Cell Line Cell Proliferation Cell Separation Cells, Cultured Embryonic Stem Cells - cytology GPI-Linked Proteins - analysis Hepatocytes - cytology Humans Induced Pluripotent Stem Cells - cytology Metalloendopeptidases - analysis Mice
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Summary:	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. [Display omitted] •CPM is a novel marker for hepatoblasts during liver development•Self-renewing hiPSC-derived CPM+ LPCs exhibit bi-potency in vitro•An efficient and convenient protocol for the generation of hiPSC-derived LPCs Miyajima, Kido, and colleagues identify CPM as a novel cell surface marker specific for liver progenitor cells (LPCs) in fetal liver. CPM+ LPCs can be isolated from hiPSC-derived immature liver cells, expanded, and differentiated to hepatocytes and cholangiocytes in vitro. CMP+ LPCs are useful for efficient large-scale production of hepatocytes and cholangiocytes.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2213-6711 2213-6711
DOI:	10.1016/j.stemcr.2015.08.008