An atlas of the aging lung mapped by single cell transcriptomics and deep tissue proteomics

Research output: Contribution to journalJournal articleResearchpeer-review

Ilias Angelidis, Lukas M Simon, Isis E Fernandez, Maximilian Strunz, Christoph H Mayr, Flavia R Greiffo, George Tsitsiridis, Meshal Ansari, Elisabeth Graf, Tim-Matthias Strom, Monica Nagendran, Tushar Desai, Oliver Eickelberg, Matthias Mann, Fabian J Theis, Herbert B Schiller

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.

Original languageEnglish
JournalNature Communications
Volume10
Issue number1
Pages (from-to)963
ISSN2041-1723
DOIs
Publication statusPublished - 27 Feb 2019
Externally publishedYes

ID: 214464264