Cytokeratin expression during mouse embryonic and early postnatal mammary gland development
Cytokeratin expression during mouse embryonic and early postnatal mammary gland development
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小鼠胚胎和产后早期乳腺发育过程中细胞角蛋白的表达
DOI：
10.1007/s00418-009-0662-5
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发表时间：
2010-02-01
影响因子：
2.3
通讯作者：
Dai, Xing
中科院分区：
文献类型：
--
作者：
Sun, Peng;Yuan, Yuanyang;Dai, Xing
细胞角蛋白是在包括乳腺上皮在内的大多数上皮细胞中发现的中间丝蛋白。已发现特异性细胞角蛋白表达标记不同的上皮细胞谱系，并且还与推定的乳腺干/祖细胞相关。然而，细胞角蛋白的表达在胚胎和出生后的乳腺发育的比较分析，目前缺乏。此外，尚不清楚胚胎发育过程中是否存在不同类型的推定乳腺干细胞/祖细胞。本研究采用免疫荧光和免疫组织化学技术，系统地比较了细胞角蛋白5（K5）、6（K6）、8（K8）、14（K14）和19（K19）在胚胎期和出生后早期小鼠乳腺中的表达。我们发现，K6（+）和K8（+）/K14（+）推定的乳腺祖细胞出现在胚胎发育过程中具有不同的时间和空间分布。此外，我们描述了一个短暂的断开K5和K14的表达，两个细胞角蛋白，往往共同表达，在产后第一周的乳腺发育。最后，我们报告说，细胞角蛋白的表达在培养的初级乳腺上皮细胞模仿，在出生后乳腺发育的早期阶段。这些研究证明了推定的乳腺干/祖细胞的胚胎起源。此外，他们提供了额外的见解，使用特定的细胞角蛋白作为乳腺上皮分化的标志物，或使用其启动子直接基因过表达或消融小鼠乳腺发育的遗传研究。
Cytokeratins are intermediate filament proteins found in most epithelial cells including the mammary epithelium. Specific cytokeratin expression has been found to mark different epithelial cell lineages and also to associate with putative mammary stem/progenitor cells. However, a comparative analysis of the expression of cytokaratins during embryonic and postnatal mammary development is currently lacking. Moreover, it is not clear whether the different classes of putative mammary stem/progenitor cells exist during embryonic development. Here, we use double/triple-label immunofluorescence and immunohistochemistry to systematically compare the expression of cytokeratin 5 (K5), cytokeratin 6 (K6), cytokeratin 8 (K8), cytokeratin 14 (K14) and cytokeratin 19 (K19) in embryonic and early postnatal mouse mammary glands. We show that K6(+) and K8(+)/K14(+) putative mammary progenitor cells arise during embryogenesis with distinct temporal and spatial distributions. Moreover, we describe a transient disconnection of the expression of K5 and K14, two cytokeratins that are often co-expressed, during the first postnatal weeks of mammary development. Finally, we report that cytokeratin expression in cultured primary mammary epithelial cells mimics that during the early stages of postnatal mammary development. These studies demonstrate an embryonic origin of putative mammary stem/progenitor cells. Moreover, they provide additional insights into the use of specific cytokeratins as markers of mammary epithelial differentiation, or the use of their promoters to direct gene overexpression or ablation in genetic studies of mouse mammary development.