An atlas of the aging lung mapped by single cell transcriptomics and deep tissue proteomics
An atlas of the aging lung mapped by single cell transcriptomics and deep tissue proteomics
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DOI：
10.1038/s41467-019-08831-9
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发表时间：
2019-02-27
影响因子：
16.6
通讯作者：
Schiller, Herbert B.
中科院分区：
文献类型：
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作者：
Angelidis, Ilias;Simon, Lukas M.;Schiller, Herbert B.
衰老促进肺功能下降和对慢性肺部疾病的易感性，这是全球第三大死亡原因。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来量化30种细胞类型中细胞活性状态的变化，并绘制年轻和老年小鼠的肺蛋白质组。我们发现，老化导致转录噪音增加，表明放松管制的表观遗传控制。我们观察到细胞类型特异性的衰老效应，发现2型肺细胞和脂肪成纤维细胞中胆固醇生物合成增加，气道上皮细胞的相对频率改变是肺衰老的标志。蛋白质组学分析揭示了老年小鼠的细胞外基质重塑，包括增加胶原IV和XVI，减少弗雷泽综合征复合物蛋白和胶原XIV。老化蛋白质组与单细胞转录组的计算整合预测了受调节蛋白质的细胞来源，并创建了老化肺的无偏倚参考图。
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.