CPM Is a Useful Cell Surface Marker to Isolate Expandable Bi-Potential Liver Progenitor Cells Derived from Human iPS Cells.
CPM Is a Useful Cell Surface Marker to Isolate Expandable Bi-Potential Liver Progenitor Cells Derived from Human iPS Cells.
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DOI：
10.1016/j.stemcr.2015.08.008
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发表时间：
2015-10-13
影响因子：
5.9
通讯作者：
Miyajima A
中科院分区：
文献类型：
--
作者：
Kido T;Koui Y;Suzuki K;Kobayashi A;Miura Y;Chern EY;Tanaka M;Miyajima A
为了开发用于大规模生产成熟肝细胞的培养系统，具有高增殖潜力的肝祖细胞（LPC）将是有利的。我们发现羧肽酶M（carboxypeptidase M，CPM）在胚胎LPCs、肝母细胞中高表达，但随着肝的成熟，其表达沿着下降。一致地，CPM表达在来自人诱导的多能干细胞（hiPSC）的肝特化期间瞬时诱导。在未成熟肝细胞阶段从分化的hiPSC分离的CPM+细胞在体外广泛增殖，并表达成肝细胞典型的一组基因。此外，CPM+细胞在诱导肝成熟后表现出成熟的肝细胞表型，并在三维培养系统中进行胆管细胞分化。这些结果表明，hiPSC衍生的CPM+细胞具有LPC的特征，具有双向增殖和分化的潜力。因此，CPM是用于分离hiPSC衍生的LPC的有用标志物，其允许开发用于产生肝细胞和胆管细胞的大规模培养系统。自更新hiPSC衍生的CPM+ LPC在体外表现出双能性一种用于产生hiPSC衍生的LPC的有效且方便的方案Miyajima，Kido及其同事将CPM鉴定为对胎肝中的肝祖细胞（LPC）具有特异性的新型细胞表面标志物。CPM+ LPC可以从hiPSC衍生的未成熟肝细胞中分离，扩增，并在体外分化为肝细胞和胆管细胞。CMP+ LPC可用于肝细胞和胆管细胞的有效大规模生产。
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. 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.