Identification and differentiation of hepatic stem cells during liver development
Identification and differentiation of hepatic stem cells during liver development
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DOI：
10.2741/1884
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发表时间：
2006-05-01
影响因子：
3.1
通讯作者：
Nakauchi, H
中科院分区：
文献类型：
--
作者：
Kamiya, A;Gonzalez, FJ;Nakauchi, H
负责维持和修复组织的干细胞存在于许多器官中。肝脏在肝切除或化学损伤后具有非凡的再生能力，但不涉及干细胞的增殖。然而，最近的研究表明，肝脏干细胞在胚胎和成人肝脏中都存在。应用荧光激活的细胞分选和原始肝祖细胞形成集落的培养体系，在发育中的肝脏中发现了一类新的细胞，其标志物为c-Met(+)CD49f(+/low)c-Kit(-)CD45(-)TER119(-)。这一类显然代表了形成包含不同肝细胞和胆管细胞的集落的细胞群体。当这类细胞被移植到受肝损伤的小鼠的脾或肝脏中时，这些细胞迁移并分化为在形态和功能上与天然细胞无法区分的肝实质细胞和胆管细胞。在妊娠中期，造血细胞从被主动脉、性腺和中肾包围的区域迁移到肝脏，并产生抑瘤素M(OSM)。与糖皮质激素结合，OSM可诱导肝脏干细胞和前体细胞成熟，包括c-Met(+)CD49f(+/low)cKit(-)CD45(-)TER119(-)类细胞。在体外控制肝脏干细胞的增殖和分化的能力将极大地有助于分析肝脏发育的机制。
Stem cells responsible for maintenance and repair of tissues are found in a number of organs. The liver's remarkable capacity to regenerate after hepatectomy or chemical-induced injury does not involve proliferation of stem cells. However, recent studies suggest that liver stem cells exist in both embryonic and adult livers. Using fluorescence-activated cell sorting and a culture system in which primitive hepatic progenitor cells form colonies, a novel class of cells with the marker profile c-Met(+)CD49f(+/low)c-Kit(-)CD45(-)TER119(-) was found in the developing liver. This class apparently represents the population of cells that form colonies containing distinct hepatocytes and cholangiocytes. When cells in this class are transplanted into the spleen or liver of mice subjected to liver injury, the cells migrate and differentiate into liver parenchymal cells and cholangiocytes that are morphologically and functionally indistinguishable from their native counterparts. During mid-gestation, hematopoietic cells migrate into the liver from a region bounded by aorta, gonad, and mesonephros and produce oncostatin M (OSM). In combination with glucocorticoid hormones, OSM induces maturation of liver stem and progenitor cells, including those of the c-Met(+)CD49f(+/low)cKit(-)CD45(-)TER119(-) class. The ability to manipulate the proliferation and differentiation of liver stem cells in vitro will greatly aid in analyzing mechanisms of liver development