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Nat Commun. 2019 Feb 27;10(1):963. doi: 10.1038/s41467-019-08831-9.

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

Author information

1
Helmholtz Zentrum München, Institute of Lung Biology and Disease, Member of the German Center for Lung Research (DZL), Munich, 85764, Germany.
2
Helmholtz Zentrum München, Institute of Computational Biology, Munich, 85764, Germany.
3
Helmholtz Zentrum München, Institute of Human Genetics, Munich, 85764, Germany.
4
Department of Internal Medicine, Division of Pulmonary and Critical Care, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, 94305, CA, USA.
5
Department of Medicine, Division of Respiratory Sciences and Critical Care Medicine, University of Colorado, Aurora, 80045, CO, USA.
6
Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Munich, 82152, Germany.
7
Helmholtz Zentrum München, Institute of Computational Biology, Munich, 85764, Germany. fabian.theis@helmholtz-muenchen.de.
8
Department of Mathematics, Technische Universität München, Munich, 85748, Germany. fabian.theis@helmholtz-muenchen.de.
9
Helmholtz Zentrum München, Institute of Lung Biology and Disease, Member of the German Center for Lung Research (DZL), Munich, 85764, Germany. herbert.schiller@helmholtz-muenchen.de.

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.

PMID:
30814501
PMCID:
PMC6393476
DOI:
10.1038/s41467-019-08831-9
[Indexed for MEDLINE]
Free PMC Article

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