PT  - JOURNAL ARTICLE
AU  - Ilias Angelidis
AU  - Lukas M. Simon
AU  - Isis E. Fernandez
AU  - Maximilian Strunz
AU  - Christoph H. Mayr
AU  - Flavia R. Greiffo
AU  - George Tsitsiridis
AU  - Elisabeth Graf
AU  - Tim-Matthias Strom
AU  - Oliver Eickelberg
AU  - Matthias Mann
AU  - Fabian J. Theis
AU  - Herbert B. Schiller
TI  - An atlas of the aging lung mapped by single cell transcriptomics and deep tissue proteomics
AID  - 10.1101/351353
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 351353
4099  - http://biorxiv.org/content/early/2018/06/20/351353.short
4100  - http://biorxiv.org/content/early/2018/06/20/351353.full
AB  - Aging promotes lung function decline and susceptibility to chronic lung diseases, which are the third leading cause of death worldwide. We used single cell transcriptomics and mass spectrometry to quantify changes in cellular activity states of 30 cell types and the tissue proteome from lungs of young and old mice. Aging led to increased transcriptional noise, indicating deregulated epigenetic control. We observed highly distinct effects of aging on cell type level, uncovering increased cholesterol biosynthesis in type-2 pneumocytes and lipofibroblasts as a novel hallmark of lung aging. Proteomic profiling revealed 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 and single cell transcriptomes predicted the cellular source of regulated proteins and created a first unbiased reference of the aging lung. The lung aging atlas can be accessed via an interactive user-friendly webtool at: https://theislab.github.io/LungAgingAtlas