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

Nature Communications
Ilias AngelidisHerbert B Schiller

Abstract

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.

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Datasets Mentioned

BETA
GSE63269
PXD012307

Methods Mentioned

BETA
Dropseq
RNA-seq
scRNA-seq
confocal
proximity
proximity ligation
solubility profiling
flow cytometry
electron microscopy
FCS

Software Mentioned

Seurat
custom
Seurat FindMarkers
RunICA
Seurat FindAllMarkers
R package limma
STAR
Perseus
Dropseq
featureCounts

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