Evidence for stem-cell niches in the tracheal epithelium
Evidence for stem-cell niches in the tracheal epithelium
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DOI：
10.1165/ajrcmb.24.6.4217
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发表时间：
2001-06-01
影响因子：
6.4
通讯作者：
Randell, SH
中科院分区：
文献类型：
--
作者：
Borthwick, DW;Shahbazian, M;Randell, SH
阐明呼吸道上皮细胞系并确定多能祖细胞作为基因治疗的靶点通常是很重要的。干细胞(S)通常存在于其分化后代空间近端的特化隔室中，但在呼吸道中尚未证明有相同的范例。我们在小鼠的气管粘膜下腺导管中发现了一组特殊的角蛋白高表达的细胞，并验证了这种假说，即被认为代表S细胞的溴脱氧尿苷(BrdU)标记保留细胞(LRC)存在于这个隔室。每周气管内吸入清洁剂或SO2致小鼠上皮损伤，持续4wk，并在损伤修复期间每48h腹腔注射BrdU一次。伤后3d和6d，在气管基底部和管腔细胞位置均可见BrdU阳性的上皮细胞。在随后的时间点(20d和95d)，LRCs定位于上气管的腺管和下气管的系统排列的病灶，通常位于软骨-软骨间连接处附近。LRCs不是肺神经内分泌细胞，异位气管切除表面上皮后，残留的腺体重建为表面样上皮，提示呼吸道上皮S细胞定位于特定的壁龛。
It is generally important to elucidate airway epithelial cell lineages and to identify multipotent progenitors as targets for gene therapy. Stem (S) cells are typically present in specialized compartments spatially proximal to their differentiated progeny, but an equivalent paradigm has not been demonstrated in the airway. We discovered a distinct population of cells displaying high levels of keratin expression in murine tracheal submucosal gland ducts, and tested the hypothesis that bromodeoxyuridine (BrdU) label-retaining cells (LRCs), thought to represent the S-cells, were present in this compartment. Mice received weekly epithelial damage by intratracheal detergent or SO2 inhalation for 4 wk and received intraperitoneal injections of BrdU every 48 h during the injury and repair period. At 3 and 6 d after injury, BrdU-positive epithelial cells were noted along the entire tracheal length in both basal and lumenal cell positions. At later time points (20 and 95 d) LRCs were localized to gland ducts in the upper trachea and to systematically arrayed foci in the lower trachea, typically near the cartilage-intercartilage junction. LRCs were not pulmonary neuroendocrine cells, Heterotopic tracheal grafts after surface epithelial removal demonstrated reconstitution of a surface-like epithelium from gland remnants, These results suggest that airway epithelial S cells are localized to specific niches.