Developing a Novel and Convenient Model for Investigating Sweat Gland Morphogenesis from Epidermal Stem Cells
Developing a Novel and Convenient Model for Investigating Sweat Gland Morphogenesis from Epidermal Stem Cells
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开发一种新颖且方便的模型来研究表皮干细胞的汗腺形态发生
DOI：
10.1155/2019/4254759
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发表时间：
2019-01-01
影响因子：
4.3
通讯作者：
Huang, Sha
中科院分区：
文献类型：
--
作者：
Hu, Tian;Xu, Yongde;Huang, Sha
汗腺由胚胎表皮发育而来。为了阐明形态发生的潜在机制，必须开发一种可靠的体外生物活性筛选测试系统。本研究采用Transwell插入物将胚胎组织与表皮干细胞（ESCs）共培养，建立了一种新型的、便捷的模型，以评估可溶性形态形成因子对体外汗腺形态发生的影响。利用该共培养系统，观察了形态学变化、组织学特征和特异性标记。初步实验发现，与胚胎足垫（EPP）组织共培养的ESCs表现为腺状结构，细胞角蛋白8 （K8）和细胞角蛋白18 （K18）阳性，而与胚胎背皮肤共培养的ESCs表现为“海螺”结构，K8、K18阴性。EPP组培养液中检测骨形态发生蛋白4 （bone morphogenetic protein 4, BMP4）和表皮生长因子（epidermal growth factor， EGF）浓度。BMP受体抑制剂能有效阻断ESC向汗腺分化，而EGF受体阻滞剂则无此作用。我们的结果显示了这种新颖和方便的模型在体内外相关性方面的明显益处。这是筛选调节汗腺形态发生机制的潜在生物活性物质的合适选择。
Sweat glands developed from the embryonic epidermis. To elucidate the underlying mechanisms of morphogenesis, a reliable in vitro test system for bioactive screening must be developed. Here, we described a novel and convenient model by coculturing embryonic tissue and epidermal stem cells (ESCs) using Transwell insert for evaluating the effects of soluble morphogens on sweat gland morphogenesis in vitro. Using this coculture system, morphological alteration, histological features, and specific markers were observed. Initial experiments revealed that ESCs cocultured with embryonic paw pad (EPP) tissue demonstrated glandular structure and cytokeratin 8 (K8) and cytokeratin 18 (K18) positive, while ESCs cocultured with embryonic dorsal skin demonstrated “sea snail” structure and K8, K18 negative. Moreover, bone morphogenetic protein 4 (BMP4) and epidermal growth factor (EGF) concentrations were detected in the medium of the EPP group. BMP receptor inhibitor could effectively block the ESC differentiation to sweat glands, while EGF receptor blocker did not show the effect. Our results showed clear benefits of this novel and convenient model in terms of in vitro-in vivo correlation. It was an appropriate alternative for screening of potential bioactives regulating the sweat gland morphogenesis mechanism.