Department of Biological Chemistry, School of Medicine, University of California, Irvine, CA 92697-1700, USA.
Histochem Cell Biol. 2010 Feb;133(2):213-21. doi: 10.1007/s00418-009-0662-5. Epub 2009 Nov 25.
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.
细胞角蛋白是存在于大多数上皮细胞中的中间丝蛋白，包括乳腺上皮细胞。特定细胞角蛋白的表达已被发现标记不同的上皮细胞谱系，并且与假定的乳腺干细胞/祖细胞相关。然而，目前缺乏对胚胎和出生后乳腺发育过程中细胞角蛋白表达的比较分析。此外，目前尚不清楚在胚胎发育过程中是否存在不同类别的假定乳腺干细胞/祖细胞。在这里，我们使用双/三重标记免疫荧光和免疫组织化学来系统比较胚胎和早期新生小鼠乳腺中细胞角蛋白 5 (K5)、细胞角蛋白 6 (K6)、细胞角蛋白 8 (K8)、细胞角蛋白 14 (K14) 和细胞角蛋白 19 (K19) 的表达。我们表明 K6(+)和 K8(+)/K14(+)假定乳腺祖细胞在胚胎发生过程中出现，具有不同的时空分布。此外，我们描述了在乳腺发育的最初几周内，两种经常共表达的细胞角蛋白 K5 和 K14 的表达发生短暂分离。最后，我们报告说，培养的原代乳腺上皮细胞中的细胞角蛋白表达模式模拟了出生后乳腺发育的早期阶段。这些研究表明假定的乳腺干细胞/祖细胞具有胚胎起源。此外，它们为特定细胞角蛋白作为乳腺上皮细胞分化的标志物的使用提供了更多的见解，或者为使用它们的启动子在小鼠乳腺发育的遗传研究中指导基因过表达或缺失提供了更多的见解。
