Helmholtz Zentrum München, Institute of Lung Biology and Disease, Member of the German Center for Lung Research (DZL), Munich, 85764, Germany.
Helmholtz Zentrum München, Institute of Computational Biology, Munich, 85764, Germany.
Nat Commun. 2019 Feb 27;10(1):963. doi: 10.1038/s41467-019-08831-9.
Aging promotes lung function decline and susceptibility to chronic lung diseases, which are the third leading cause of death worldwide. Here, we use single cell transcriptomics and mass spectrometry-based proteomics to quantify changes in cellular activity states across 30 cell types and chart the lung proteome of young and old mice. We show that aging leads to increased transcriptional noise, indicating deregulated epigenetic control. We observe cell type-specific effects of aging, uncovering increased cholesterol biosynthesis in type-2 pneumocytes and lipofibroblasts and altered relative frequency of airway epithelial cells as hallmarks of lung aging. Proteomic profiling reveals extracellular matrix remodeling in old mice, including increased collagen IV and XVI and decreased Fraser syndrome complex proteins and collagen XIV. Computational integration of the aging proteome with the single cell transcriptomes predicts the cellular source of regulated proteins and creates an unbiased reference map of the aging lung.
衰老是导致肺功能下降和易患慢性肺部疾病的主要原因之一，后者是全球范围内的第三大致死原因。在这里，我们使用单细胞转录组学和基于质谱的蛋白质组学技术，定量分析了 30 种细胞类型中细胞活性状态的变化，并绘制了年轻和老年小鼠的肺部蛋白质组图谱。结果表明，衰老是导致转录噪声增加的原因，表明表观遗传控制失调。我们观察到了衰老的细胞类型特异性效应，揭示了 2 型肺泡细胞和脂肪成纤维细胞中胆固醇生物合成增加，以及气道上皮细胞相对频率改变是肺部衰老的特征。蛋白质组学分析揭示了老年小鼠细胞外基质的重塑，包括胶原蛋白 IV 和 XVI 增加，Fraser 综合征复合物蛋白和胶原蛋白 XIV 减少。通过将衰老蛋白质组与单细胞转录组进行计算整合，预测了受调控蛋白的细胞来源，并创建了一个无偏倚的衰老肺部参考图谱。
