Terminal bronchioles harbor a unique airway stem cell population that localizes to the bronchoalveolar duct junction
Terminal bronchioles harbor a unique airway stem cell population that localizes to the bronchoalveolar duct junction
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DOI：
10.1016/s0002-9440(10)64169-7
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发表时间：
2002-07-01
影响因子：
6
通讯作者：
Stripp, BR
中科院分区：
文献类型：
--
作者：
Giangreco, A;Reynolds, SD;Stripp, BR
促进终末细支气管更新的细胞机制仍未明确。我们以前的研究发现，表达污染物抗性的Clara细胞分泌蛋白(CCSP)的干细胞定位于神经上皮体(NEB)，有助于近端细支气管上皮的更新。然而，NEB相关干细胞的激活不太可能有助于终末细支气管上皮的更新，因为该部位的NEB很少。这项研究的目的是确定在Clara细胞耗尽后，有助于终末细支气管更新的细胞的位置和属性。污染物抗性CCSP表达细胞定位于支气管肺泡管连接处(BADJ)，有助于修复表型多样的上皮细胞。CCSP表达的细胞组成了终末细支气管壁修复的主要增殖细胞群，并包括一群标记保留细胞，表明它们保持了干细胞群的特征。此外，CCSP和NEB特异性标记物降钙素基因相关肽的免疫组织化学共定位研究表明，BADJ相关CCSP表达干细胞的功能独立于NEB微环境。这些研究确定了BADJ相关的、NEB不依赖的、表达CCSP的终末干细胞群。并支持区域特异性干细胞壁龛维持上皮细胞功能的观点。损伤后的多样性。
Cellular mechanisms contributing to renewal of terminal bronchioles remain, poorly defined. Our previous studies identified pollutant-resistant Clara cell secretory protein (CCSP)-expressing stem cells that localize to the neuroepithelial body (NEB) and contribute to renewal of the proximal bronchiolar epithelium. However, activation of NEB-associated stem cells is unlikely to contribute to renewal of terminal bronchiolar epithelium because of the paucity of NEBs at this location. Goals of this study were to determine the location and properties of cells contributing to renewal of terminal bronchioles after Clara cell depletion. Pollutant-resistant CCSP-expressing cells were identified that localized to the bronchoalveolar duct junction (BADJ) and contribute to restoration of a phenotypically diverse epithelium. CCSP-expressing cells comprise the predominant proliferative population in initial terminal bronchiolar repair and include a population of label-retaining cells suggesting that they maintain characteristics of a stem cell population. Furthermore, immunohistochemical co-localization studies involving CCSP and the NEB-specific marker calcitonin gene-related peptide indicate that BADJ-associated CCSP-expressing stem cells function independently of NEB microenvironments. These studies identify a BADJ-associated, NEB-independent, CCSP-expressing stem cell population in terminal. bronchioles and support the notion that regiospecific stein cell niches function to maintain epithelial. diversity after injury.