Masson Neil M, Currie Ian S, Terrace John D, Garden O James, Parks Rowan W, Ross James A
Tissue Injury and Repair Group, Department of Clinical and Surgical Sciences (Surgery), University of Edinburgh Medical School, Edinburgh, EH16 4SB, UK.
Am J Physiol Gastrointest Liver Physiol. 2006 Jul;291(1):G45-54. doi: 10.1152/ajpgi.00465.2005.
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-4alpha. 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.
肝祖细胞在病变肝脏的再生过程中发挥着重要作用。在啮齿动物中，形成肝细胞或胆管细胞的祖细胞可通过干细胞标志物Thy-1来识别。本研究的目的是确定在人类胎儿肝脏中是否能识别出表达Thy-1的祖细胞。对妊娠中期的人类胎儿肝脏进行Thy-1、细胞角蛋白18和19、波形蛋白、CD34、CD45和纤维蛋白原的免疫染色。使用荧光激活细胞分选（FACS）纯化Thy-1+和Thy-1+CD34+细胞群。采用免疫荧光和mRNA表达来检测纯化干细胞的双能性。我们发现Thy-1+细胞集中在门管区，但也散在于实质中。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，另一些则共表达纤维蛋白原和细胞角蛋白19。RT-PCR表明，Thy-1+细胞表达Thy-1、细胞角蛋白18和细胞角蛋白19的mRNA，而Thy-1+CD34+细胞表达甲胎蛋白、转铁蛋白和肝细胞核因子-4α的mRNA。在胎儿肝脏中鉴定出Thy-1+细胞。这些细胞表达多种谱系标志物，包括胆管和肝细胞蛋白及mRNA的共表达。这些数据表明，Thy-1是人类胎儿肝脏中肝干细胞的标志物。
