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Angelidis, I. ; Simon, L. ; Fernandez, I.E. ; Strunz, M. ; Mayr, C. ; Greiffo, F.R. ; Tsitsiridis, G. ; Ansari, M. ; Graf, E. ; Strom, T.M. ; Nagendran, M.* ; Desai, T.* ; Eickelberg, O.* ; Mann, M.* ; Theis, F.J. ; Schiller, H. B.

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

Nat. Commun. 10:963 (2019)
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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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Publication type Article: Journal article
Document type Scientific Article
Keywords Gene-expression; Rna-seq; Spatial Transcriptomics; Mechanisms; Beta; Dysfunction; Hallmarks; Diseases; Decorin; Site
Language
Publication Year 2019
HGF-reported in Year 2019
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 10, Issue: 1, Pages: , Article Number: 963 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) German Center for Lung Research (DZL)
Institute of Computational Biology (ICB)
Institute of Lung Health and Immunity (LHI)
Institute of Human Genetics (IHG)
POF-Topic(s) 80000 - German Center for Lung Research
30205 - Bioengineering and Digital Health
30202 - Environmental Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Research field(s) Lung Research
Enabling and Novel Technologies
Genetics and Epidemiology
PSP Element(s) G-501800-810
G-503800-001
G-501600-001
G-500700-001
DOI 10.1038/s41467-019-08831-9
WOS ID WOS:000459803200001
Scopus ID 85062396680
PubMed ID 30814501
Erfassungsdatum 2019-03-13
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