The existence of multipotent stem cells with epithelial-mesenchymal transition features in the human liver bud.

The existence of multipotent stem cells with epithelial-mesenchymal transition features in the human liver bud.
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DOI:
10.1016/j.biocel.2010.09.009
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发表时间:
2010-12
影响因子:
4
通讯作者:
Hu, Yi-Ping
Hu, Yi-Ping
中科院分区:
生物学2区
文献类型:
--
作者:
Su, Juan;You, Pu;Li, Wen-Lin;Tao, Xin-Rong;Zhu, Hai-Ying;Yao, Yu-Cheng;Yu, Hong-Yu;Han, Qing-Wang;Yu, Bing;Liu, Fang-Xia;Xu, Jun;Lau, Joseph T. Y.;Hu, Yi-Ping

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在胚胎发育早期,肝芽由前肠内胚层产生,是未来肝脏三维结构形成的开端。虽然与这一发育阶段相关的基因表达谱已经得到了很好的探索,但详细的细胞事件尚不清楚。上皮-间质转化(EMT)被认为是早期脊椎动物胚胎细胞迁移的必要条件,但很少在人类肝脏发育中得到证实。在这项研究中,我们试图在人肝芽中识别具有干细胞和EMT特征的细胞群。我们的原位研究表明,EMT的表型发生在人类肝脏发育的开始,伴随着EMT相关基因的上调。建立了人肝芽源性干细胞系(hLBSC),该细胞系不仅表达间充质细胞和肝细胞特异性基因,还表达八聚体结合蛋白4 (OCT4)和Nanog。将hLBSC置于合适的培养基中,体外分化为肝细胞、脂肪细胞、成骨细胞样细胞和神经元样细胞。当移植到经四氯化碳预处理的严重联合免疫缺陷小鼠体内时,hLBSC植入肝实质并增殖。这些数据表明,人肝芽中存在具有干细胞和emt样特性的细胞群,它们可能在肝脏空间结构构建的开始阶段发挥重要作用。
During early stage of embryonic development, the liver bud, arising from the foregut endoderm, is the beginning for the formation of future liver three-dimensional structure. While the gene expression profiles associated with this developmental stage have been well explored, the detailed cellular events are not as clear. Epithelial-mesenchymal transition (EMT) was thought to be essential for cell migration in the early vertebrate embryo but seldom demonstrated in human liver development. In this study, we tried to identify the cell populations with both stem cell and EMT features in the human liver bud. Our in situ studies show that the phenotype of EMT occurs at initiation of human liver development, accompanied by up-regulation of EMT associated genes. A human liver bud derived stem cell line (hLBSC) was established, which expressed not only genes specific to both mesenchymal cells and hepatic cells, but also Octamer-binding protein 4 (OCT4) and Nanog. Placed in appropriate media, hLBSC differentiated into hepatocytes, adipocytes, osteoblast-like cells and neuron-like cells in vitro. When transplanted into severe combined immunodeficiency mice pre-treated by carbon tetrachloride, hLBSC engrafted into the liver parenchyma and proliferated. These data suggest that there are cell populations with stem cell and EMT-like properties in the human liver bud, which may play an important role in the beginning of the spatial structure construction of the liver.
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发表时间: 2002-01-07
期刊: The Journal of cell biology
影响因子: --
作者:
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