Diversification of Cell Lineages in Ureter Development
Diversification of Cell Lineages in Ureter Development
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DOI：
10.1681/asn.2016080849
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发表时间：
2017-06-01
影响因子：
13.6
通讯作者：
Kispert, Andreas
中科院分区：
文献类型：
--
作者：
Bohnenpoll, Tobias;Feraric, Sarah;Kispert, Andreas
哺乳动物输尿管由间充质壁和内层上皮组成，间充质壁由平滑肌细胞和周围的图尼卡外膜和固有层的纤维细胞组成，内层上皮由基底层、中层和表层细胞组成。这些细胞类型是如何从多能祖细胞中产生的，目前还知之甚少。在这里，我们进行了标记物分析，细胞增殖试验，和遗传谱系追踪，以确定发展和成熟的小鼠输尿管间充质和上皮细胞类型的谱系关系和限制。在胚胎第12.5天（E），间充质前体库开始细分为内室和外室，到E13.5时，内室和外室分别开始表达平滑肌前体和外膜纤维细胞的标志物。平滑肌前体细胞进一步分化为与输尿管上皮直接相邻的固有层细胞，并从E16.5开始分化为平滑肌细胞。输尿管的未定型上皮祖细胞在E14.5分化为中间细胞。E15.5层化为两层细胞，E18.5层化为三层细胞，中间细胞分化为基底细胞和表层细胞。在稳态，所有上皮细胞和间充质细胞类型的增殖仍然很低，但中间细胞仍然产生基底细胞，而基底细胞只分裂成基底细胞。这些研究提供了一个框架，以进一步确定细胞分化的分子机制，在组织的发展输尿管。
The mammalian ureter consists of a mesenchymal wall composed of smooth muscle cells and surrounding fibrocytes of the tunica adventitia and the lamina propria and an inner epithelial lining composed of layers of basal, intermediate, and superficial cells. How these cell types arise from multipotent progenitors is poorly understood. Here, we performed marker analysis, cell proliferation assays, and genetic lineage tracing to define the lineage relations and restrictions of the mesenchymal and epithelial cell types in the developing and mature mouse ureter. At embryonic day (E) 12.5, the mesenchymal precursor pool began to subdivide into an inner and outer compartment that began to express markers of smooth muscle precursors and adventitial fibrocytes, respectively, by E13.5. Smooth muscle precursors further diversified into lamina propria cells directly adjacent to the ureteric epithelium and differentiated smooth muscle cells from E16.5 onwards. Uncommitted epithelial progenitors of the ureter differentiated into intermediate cells at E14.5. After stratification into two layers at E15.5 and three cell layers at E18.5, intermediate cells differentiated into basal cells and superficial cells. In homeostasis, proliferation of all epithelial and mesenchymal cell types remained low but intermediate cells still gave rise to basal cells, whereas basal cells divided only into basal cells. These studies provide a framework to further determine the molecular mechanisms of cell differentiation in the tissues of the developing ureter.