Basal cells are a multipotent progenitor capable of renewing the bronchial epithelium
Basal cells are a multipotent progenitor capable of renewing the bronchial epithelium
复制标题
DOI：
10.1016/s0002-9440(10)63147-1
复制
发表时间：
2004-02-01
影响因子：
6
通讯作者：
Stripp, BR
中科院分区：
文献类型：
--
作者：
Hong, KU;Reynolds, SD;Stripp, BR
在肺发育的假腺期向管状期过渡期间，肺上皮细胞与支气管和细支气管型呼吸道谱系的结合发生，这表明在成年期促进上皮维持的干细胞和前体细胞的特性方面存在区域差异。我们先前明确了Clara细胞分泌蛋白表达(CE)细胞在损伤后细支气管呼吸道上皮更新中的关键作用。尽管CE细胞也是维持支气管呼吸道上皮的主要前体细胞，CE细胞损伤是通过一种涉及招募第二前体细胞群体的机制来解决的，我们现在确定第二前体细胞群体是GSI-B-4反应性的、表达细胞角蛋白-14的基底细胞。通过对LacZ标记细胞克隆内的细胞表型分析，这些细胞显示出多潜能分化能力。克隆来自表达K14的细胞，通过配体可调节的Cre重组酶介导的rosa26重组底物等位基因的基因组重排，以特定细胞类型的方式标记。我们的结论是，基底细胞代表了一种替代的多能前体细胞群体，而前体细胞的选择取决于呼吸道损伤的类型。
Commitment of the pulmonary epithelium to bronchial and bronchiolar airway lineages occurs during the transition from pseudoglandular to cannalicular phases of lung development, suggesting that regional differences exist with respect to the identity of stem and progenitor cells that contribute to epithelial maintenance in adulthood. We previously defined a critical role for Clara cell secretory protein-expressing (CE) cells in renewal of bronchiolar airway epithelium following injury. Even though CE cells are also the principal progenitor for maintenance of the bronchial airway epithelium, CE cell injury is resolved through a mechanism involving recruitment of a second progenitor cell population that we now identify as a GSI-B-4 reactive, cytokeratin-14-expressing basal cell. These cells exhibit multipotent differentiation capacity as assessed by analysis of cellular phenotype within clones of LacZ-tagged cells. Clones were derived from K14-expressing cells tagged in a cell-type-specific fashion by ligand-regulable Cre recombinase-mediated genomic rearrangement of the ROSA26 recombination substrate allele. We conclude that basal cells represent an alternative multipotent progenitor cell population of bronchial airways and that progenitor cell selection is dictated by the type of airway injury.