Flow cytometric isolation of endodermal progenitors from mouse salivary gland differentiate into hepatic and pancreatic lineages
Flow cytometric isolation of endodermal progenitors from mouse salivary gland differentiate into hepatic and pancreatic lineages
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DOI：
10.1002/hep.20063
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发表时间：
2004-03-01
期刊：
影响因子：
13.5
通讯作者：
Endo, F
中科院分区：
文献类型：
--
作者：
Hisatomi, Y;Okumura, K;Endo, F
实验性损伤有助于诱导组织干细胞，这些细胞在正常条件下可能以少量存在。唾液腺起源于内胚层，由腺泡和导管上皮细胞组成，具有外分泌功能。在唾液腺导管结扎后，腺泡细胞由于凋亡而消失，导管上皮随后增殖。在这项研究中，我们分析了组织干细胞的小鼠唾液腺导管结扎诱导的免疫组织化学和流式细胞仪。我们通过荧光激活细胞分选法从成年小鼠唾液腺中分选Sca-1（+）/c-Kit（+）组分。分选的细胞显然是同质的，并被指定为小鼠唾液腺来源的祖细胞（mSGPs）。当在基质胶中培养时，mSGP细胞分化成肝谱系。在存在胰高血糖素样肽-1（GLP-1）的球形培养物中，这些细胞分化为胰腺内分泌谱系。当球体的mSGP，直径20至30微米，通过门静脉移植到肝脏，细胞整合到肝索和表达白蛋白和α 1-抗胰蛋白酶，这表明他们已经分化成肝型细胞。此外，还出现了由mSGP细胞形成的导管样结构，其上皮细胞为细胞角蛋白19阳性。总之，基于组织学证据的荧光激活细胞分选（FACS）在分离唾液腺成体组织干细胞方面是有效的。内胚层来源的组织干细胞（例如，肝卵圆细胞、胰腺上皮祖细胞和唾液腺祖细胞）在它们的分子标记物和组织定位方面具有相似性。我们的研究结果表明，在内胚层来源的器官中存在共同的组织干细胞。
Experimental injury is useful to induce tissue stem cells, which may exist in small numbers under normal conditions. The salivary glands originate from the endoderm and consist of acinar and ductal epithelial cells, which have exocrine function. After salivary gland duct ligation, acinar cells disappear as a result of apoptosis, and duct epithelium subsequently proliferates. In this study, we analyzed the tissue stem cells induced by salivary gland duct ligation in mice using immunohistochemistry and flow cytometry. We sorted the Sca-l(+)/c-Kit(+) fraction from adult mice salivary glands by way of fluorescence-activated cell sorting. The sorted cells were apparently homogeneous and were designated mouse salivary gland-derived progenitors (mSGPs). mSGP cells differentiated into a hepatic lineage when cultured in matrigel. In spherical culture in the presence of glucagon-like peptide-1 (GLP-1), these cells differentiated into a pancreatic endocrine lineage. When spheroidal bodies of mSGP, 20 to 30 mum in diameter, were transplanted into liver via the portal vein, the cells integrated into hepatic cords and expressed albumin and alpha1-antitrypsin, suggesting that they had differentiated into hepatic-type cells. Moreover, ductlike structures formed by mSGP cells also appeared, epithelial cells of which were positive for cytokeratin 19. In conclusion, fluorescence-activated cell sorting (FACS) based on histologic evidence is efficient in isolating adult tissue stem cells of the salivary gland. Tissue stem cells of endodermal origin (e.g., hepatic oval cells, pancreatic epithelial progenitor cells, and salivary gland progenitor cells) have similarities in their molecular markers and tissue location. Our findings suggest the existence of common tissue stem cells in endoderm-derived organs.