Hepatic progenitor cells in human fetal liver express the oval cell marker Thy-1
Hepatic progenitor cells in human fetal liver express the oval cell marker Thy-1
复制标题
DOI：
10.1152/ajpgi.00465.2005
复制
发表时间：
2006-07-01
影响因子：
4.5
通讯作者：
Ross, James A.
中科院分区：
文献类型：
--
作者：
Masson, Neil M.;Currie, Ian S.;Ross, James A.
肝祖细胞在病变肝脏的再生中起着重要作用。在啮齿类动物中，形成肝细胞或胆管细胞的祖细胞通过干细胞标志物Thy-1鉴定。本研究的目的是确定是否可以在人胎肝中鉴定出表达Thy-1的祖细胞。孕中期人胎肝进行免疫染色的Thy-1，细胞角蛋白18和19，波形蛋白，CD 34，CD 45，和纤维蛋白原。使用荧光激活细胞分选（FACS）纯化Thy-1（+）和Thy-1（+）CD 34（+）群体。免疫荧光和mRNA表达被用来检查纯化的干细胞的双能性。Thy-1（+）细胞主要集中在汇管区，但也散在分布于肝实质。在FACS制备的细胞中，0.18-3.08%（中位数0.65%，n = 14）的细胞为Thy-1（+）。免疫表型分析显示，一些Thy-1（+）细胞共表达细胞角蛋白18和19，其他人，纤维蛋白原和细胞角蛋白19。RT-PCR显示Thy-1（+）细胞表达Thy-1、细胞角蛋白18和细胞角蛋白19的mRNA，Thy-1（+）CD 34（+）细胞表达甲胎蛋白、转铁蛋白和肝细胞核因子-4 α的mRNA。在胎肝中鉴定出Thy-1（+）细胞。这些细胞表达几种谱系标记物，包括胆汁和肝细胞蛋白质和mRNA的共表达。这些数据表明，Thy-1是人胎肝中肝干细胞的标志物。
Hepatic progenitor cells play a major role in regenerating diseased liver. In rodents, progenitors forming hepatocytes or cholangiocytes are identified by the stem cell marker Thy-1. The aim of this study was to ascertain whether progenitor cells expressing Thy-1 could be identified in human fetal liver. Midtrimester human fetal liver was immunostained for Thy-1, cytokeratins 18 and 19, vimentin, CD34, CD45, and fibrinogen. Thy-1(+) and Thy-1(+)CD34(+) populations were purified using fluorescence-activated cell sorting (FACS). Immunofluorescence and mRNA expression were used to examine the bipotential nature of purified stem cells. We found that Thy-1(+) cells were concentrated in portal tracts but were also scattered in parenchyma. In FACS-prepared cells, 0.18-3.08% (median 0.65%, n = 14) of cells were Thy-1(+). Immunophenotyping revealed that some Thy-1(+) cells coexpressed cytokeratins 18 and 19, others, fibrinogen and cytokeratin 19. RT-PCR demonstrated that Thy-1(+) cells expressed mRNA for Thy-1, cytokeratin 18, and cytokeratin 19, and Thy-1(+)CD34(+) cells expressed mRNA for alpha-fetoprotein, transferrin, and hepatocyte nuclear factor-4 alpha. Thy-1(+) cells were identified in fetal liver. These cells expressed several lineage markers, including coexpression of biliary and hepatocellular proteins and mRNA. These data suggest that Thy-1 is a marker of liver stem cells in human fetal liver.