Clara cell secretory protein-expressing cells of the airway neuroepithelial body microenvironment include a label-retaining subset and are critical for epithelial renewal after progenitor cell depletion
Clara cell secretory protein-expressing cells of the airway neuroepithelial body microenvironment include a label-retaining subset and are critical for epithelial renewal after progenitor cell depletion
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DOI：
10.1165/ajrcmb.24.6.4498
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发表时间：
2001-06-01
影响因子：
6.4
通讯作者：
Stripp, BR
中科院分区：
文献类型：
--
作者：
Hong, KU;Reynolds, SD;Stripp, BR
干细胞的潜力，有助于重建正常的细支气管上皮尚未明确证明，我们以前建立的神经上皮小体（NEB）隔离再生细胞，有助于细支气管再生后，选择性化学耗竭克拉拉细胞，一个主要的祖细胞群体。根据化学消融后的增殖潜力鉴定了两种候选干细胞：Clara细胞的耐污染亚群，其保留了Clara细胞分泌蛋白（CCSP）的表达（变体CCSP表达[CE]细胞或vCE细胞）和降钙素基因相关肽（CGRP）表达肺神经内分泌细胞（PNEC）。在本研究中，两个群体的标记保留细胞内的NEB：CGRP表达细胞和CE细胞的亚群。为了研究CE和CGRP表达细胞对上皮更新的贡献，通过对在小鼠CCSP启动子的调控下表达单纯疱疹病毒胸苷激酶的转基因小鼠急性给予更昔洛韦来消融CE细胞。CGRP免疫反应性PNEC增殖后消耗CE细胞，但不能重新填充CE细胞耗尽的气道，这些结果支持的概念，即vCE细胞代表气道干细胞或干细胞的维持是至关重要的，并表明PNEC是不足以上皮更新。
Stem cells with potential to contribute to the re-establishment of the normal bronchiolar epithelium have not been definitively demonstrated, We previously established that neuroepithelial bodies (NEBs) sequester regenerative cells that contribute to bronchiolar regeneration after selective chemical depletion of Clara cells, a major progenitor cell population. Two candidate stem cells were identified on the basis of proliferative potential after chemical ablation: a pollutant-resistant subpopulation of Clara cells that retain their expression of Clara cell secretory protein (CCSP) (variant CCSP-expressing [CE] cells or vCE cells) and calcitonin gene-related peptide (CGRP)-expressing pulmonary neuroendocrine cells (PNECs). In the present study, two populations of label-retaining cells were identified within the NEB: CGRP-expressing cells and a subpopulation of CE cells. To investigate contributions made by CE and CGRP-expressing cells to epithelial renewal, CE cells were ablated through acute administration of ganciclovir to transgenic mice expressing herpes simplex virus thymidine kinase under the regulatory control of the mouse CCSP promoter. CGRP-immunoreactive PNECs proliferated after depletion of CE cells, yet were unable to repopulate CE cell-depleted airways, These results support the notion that vCE cells represent either an airway stem cell or are critical for stem cell maintenance, and suggest that PNECs are not sufficient for epithelial renewal.