Identification and Characterization of Mesenchymal-Epithelial Progenitor-Like Cells in Normal and Injured Rat Liver
Identification and Characterization of Mesenchymal-Epithelial Progenitor-Like Cells in Normal and Injured Rat Liver
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DOI：
10.1016/j.ajpath.2014.08.029
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发表时间：
2015-01-01
影响因子：
6
通讯作者：
Dabeva, Mariana D.
中科院分区：
文献类型：
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作者：
Liu, Daqing;Yovchev, Mladen I.;Dabeva, Mariana D.
在正常大鼠肝脏中，胸腺细胞抗原1（Thy 1）在成纤维细胞/肌成纤维细胞和一些血液祖细胞中表达。Thy 1表达细胞在受损的肝再生过程中也在肝脏中积累。这些细胞的起源和性质还不清楚。通过使用RT-PCR分析和免疫荧光显微镜，我们描述了罕见的Thy 1（+）细胞在正常动物的肝小叶中的存在，偶尔形成高达20个细胞的小集合。这些细胞构成了一小部分（1.7%至1.8%）的非实质细胞，并揭示了混合间充质上皮表型，表达E-钙粘蛋白，细胞角蛋白18，和结蛋白。体外间充质-上皮Thy 1（+）细胞最有效的促分裂原是Thy 1（+）细胞不产生的炎性细胞因子干扰素γ、IL-1和血小板衍生生长因子-BB。Thy 1（+）细胞表达所有典型的间充质干细胞和肝祖细胞标志物，并产生维持卵圆细胞生长和分化的蛋白质的生长因子和细胞因子mRNA（Hgf、IL 6、Tgfa和Tweak）。在适当的条件下，间充质上皮细胞在体外分化为肝细胞样细胞。在这项研究中，我们发现，成年大鼠肝脏窝藏一个小池的内源性间充质上皮细胞以前没有认识到。在静止状态下，这些细胞表达间充质和上皮细胞标志物。它们表现为具有双重表型的肝干细胞/祖细胞，表现出高可塑性和持久的增殖活性。
In normal rat Liver, thymocyte antigen 1 (Thy1) is expressed in fibroblasts/myofibroblasts and in some blood progenitor cells. Thy1-expressing cells also accumulate in the Liver during impaired liver regeneration. The origin and nature of these cells are not well understood. By using RT-PCR analysis and immunofluorescence microscopy, we describe the presence of rare Thy1(+) cells in the liver lobule of normal animals, occasionally forming small collections of up to 20 cells. These cells constitute a small portion (1.7% to 1.8%) of nonparenchymal cells and reveal a mixed mesenchymal-epithelial phenotype, expressing E-cadherin, cytokeratin 18, and desmin. The most potent mitogens for mesenchymal-epithelial Thy1(+) cells in vitro are the inflammatory cytokines interferon gamma, IL-1, and platelet-derived growth factor-BB, which are not produced by Thy1(+) cells. Thy1(+) cells express all typical mesenchymal stem cell and hepatic progenitor cell markers and produce growth factor and cytokine mRNA (Hgf, IL6, Tgfa, and Tweak) for proteins that maintain oval cell growth and differentiation. Under appropriate conditions, mesenchymal-epithelial cells differentiate in vitro into hepatocyte-like cells. In this study, we show that the adult rat Liver harbors a small pool of endogenous mesenchymal-epithelial cells not recognized previously. In the quiescent state, these cells express both mesenchymal and epithelial cell markers. They behave like hepatic stem cells/progenitors with dual phenotype, exhibiting high plasticity and Long-lasting proliferative activity.