[PDF][PDF] CPM is a useful cell surface marker to isolate expandable bi-potential liver progenitor cells derived from human iPS cells

T Kido, Y Koui, K Suzuki, A Kobayashi, Y Miura… - Stem Cell Reports, 2015 - cell.com
T Kido, Y Koui, K Suzuki, A Kobayashi, Y Miura, EY Chern, M Tanaka, A Miyajima
Stem Cell Reports, 2015cell.com
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 …
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.
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