Department of Pediatrics, Division of Cell Biology, National Jewish Health, Denver, Colorado, USA.
Am J Pathol. 2010 Jul;177(1):362-76. doi: 10.2353/ajpath.2010.090870. Epub 2010 Jun 3.
Analysis of lineage relationships in the naphthalene-injured tracheal epithelium demonstrated that two multipotential keratin 14-expressing cells (K14ECs) function as progenitors for Clara and ciliated cells. These K14EC were distinguished by their self-renewal capacity and were hypothesized to reside at the stem and transit amplifying tiers of a tissue-specific stem cell hierarchy. In this study, we used gene expression and histomorphometric analysis of the steady-state and naphthalene-injured trachea to evaluate the predictions of this model. We found that the steady-state tracheal epithelium is maintained by two progenitor cell pools, secretory and basal cells, and the latter progenitor pool is further divided into two subsets, keratin 14-negative and -positive. After naphthalene-mediated depletion of the secretory and ciliated cell types, the two basal cell pools coordinate to restore the epithelium. Both basal cell types up-regulate keratin 14 and generate a broadly distributed, abundant, and highly mitotic cell pool. Furthermore, basal cell proliferation is associated with generation of differentiated Clara and ciliated cells. The uniform distribution of basal cell progenitors and of their differentiated progeny leads us to propose that the hierarchical organization of tracheal reparative cells be revised to include a facultative basal cell progenitor pool.
分析萘损伤的气管上皮细胞谱系关系表明，两个多能角蛋白 14 表达细胞（K14EC）作为 Clara 和纤毛细胞的祖细胞。这些 K14EC 因其自我更新能力而被区分，并被假设位于组织特异性干细胞层级的干细胞和过渡扩增层。在这项研究中，我们使用稳态和萘损伤气管的基因表达和组织形态计量分析来评估该模型的预测。我们发现，稳态气管上皮由两个祖细胞池，分泌细胞和基底细胞维持，后者祖细胞池进一步分为两个亚群，角蛋白 14 阴性和阳性。在萘介导的分泌细胞和纤毛细胞类型耗竭后，两个基底细胞池协调恢复上皮。两种基底细胞类型均上调角蛋白 14 并产生广泛分布、丰富且高度有丝分裂的细胞池。此外，基底细胞增殖与分化的 Clara 和纤毛细胞的产生相关。基底细胞祖细胞及其分化后代的均匀分布促使我们提出，气管修复细胞的层次组织应进行修订，以包括一个兼性基底细胞祖细胞池。
