Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Biocellvia, 10 rue Grignan, Marseille, 13001, France.
Sci Rep. 2020 Jun 26;10(1):10490. doi: 10.1038/s41598-020-66966-y.
Tissue stem cell exhaustion is a key hallmark of aging, and in this study, we characterised its manifestation in the distal lung. We compared the lungs of 3- and 22-month old mice. We examined the gross morphological changes in these lungs, the density and function of epithelial progenitor populations and the epithelial gene expression profile. Bronchioles became smaller in their cross-sectional area and diameter. Using long-term EdU incorporation analysis and immunohistochemistry, we found that bronchiolar cell density remained stable with aging, but inferred rates of bronchiolar club progenitor cell self-renewal and differentiation were reduced, indicative of an overall slowdown in cellular turnover. Alveolar Type II progenitor cell density and self-renewal were maintained per unit tissue area with aging, but rates of inferred differentiation into Type I cells, and indeed overall density of Type I cells was reduced. Microarray analysis revealed age-related changes in multiple genes, including some with roles in proliferation and differentiation, and in IGF and TGFβ signalling pathways. By characterising how lung stem cell dynamics change with aging, this study will elucidate how they contribute to age-related loss of pulmonary function, and pathogenesis of common age-related pulmonary diseases.
组织干细胞耗竭是衰老的一个关键标志，在这项研究中，我们研究了其在远端肺部的表现。我们比较了 3 月龄和 22 月龄小鼠的肺部。我们检查了这些肺部的大体形态变化、上皮祖细胞群体的密度和功能以及上皮基因表达谱。细支气管的横截面积和直径变小。通过长期 EdU 掺入分析和免疫组织化学，我们发现随着年龄的增长，细支气管细胞密度保持稳定，但推断出的支气管球祖细胞自我更新和分化的速度降低，表明细胞更替总体放缓。肺泡 II 型祖细胞密度和自我更新随年龄的增长而维持，但推断分化为 I 型细胞的速度以及 I 型细胞的总体密度降低。微阵列分析显示出多个基因的年龄相关变化，包括一些与增殖和分化以及 IGF 和 TGFβ 信号通路有关的基因。通过描述肺部干细胞动力学如何随年龄变化，这项研究将阐明它们如何导致与年龄相关的肺功能丧失以及常见与年龄相关的肺部疾病的发病机制。
