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

Ilias Angelidis, Lukas M. Simon, Isis E. Fernandez, Maximilian Strunz, Christoph H. Mayr, Flavia R. Greiffo, George Tsitsiridis, Elisabeth Graf, Tim-Matthias Strom, Oliver Eickelberg, Matthias Mann, Fabian J. Theis, Herbert B. Schiller
doi: https://doi.org/10.1101/351353
Ilias Angelidis
1Helmholtz Zentrum München, Institute of Lung Biology and Disease, Member of the German Center for Lung Research (DZL), Munich, Germany
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Lukas M. Simon
2Helmholtz Zentrum München, Institute of Computational Biology, Munich, Germany
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Isis E. Fernandez
1Helmholtz Zentrum München, Institute of Lung Biology and Disease, Member of the German Center for Lung Research (DZL), Munich, Germany
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Maximilian Strunz
1Helmholtz Zentrum München, Institute of Lung Biology and Disease, Member of the German Center for Lung Research (DZL), Munich, Germany
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Christoph H. Mayr
1Helmholtz Zentrum München, Institute of Lung Biology and Disease, Member of the German Center for Lung Research (DZL), Munich, Germany
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Flavia R. Greiffo
1Helmholtz Zentrum München, Institute of Lung Biology and Disease, Member of the German Center for Lung Research (DZL), Munich, Germany
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George Tsitsiridis
2Helmholtz Zentrum München, Institute of Computational Biology, Munich, Germany
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Elisabeth Graf
3Helmholtz Zentrum München, Institute of Human Genetics, Munich, Germany
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Tim-Matthias Strom
3Helmholtz Zentrum München, Institute of Human Genetics, Munich, Germany
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Oliver Eickelberg
4University of Colorado, Department of Medicine, Division of Respiratory Sciences and Critical Care Medicine, Denver, CO, USA
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Matthias Mann
5Max Planck Institute of Biochemistry, Department of Proteomics and Signal Transduction, Martinsried, Germany
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Fabian J. Theis
2Helmholtz Zentrum München, Institute of Computational Biology, Munich, Germany
6Department of Mathematics, Technische Universität München, Munich, Germany
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  • For correspondence: fabian.theis@helmholtz-muenchen.de herbert.schiller@helmholtz-muenchen.de
Herbert B. Schiller
1Helmholtz Zentrum München, Institute of Lung Biology and Disease, Member of the German Center for Lung Research (DZL), Munich, Germany
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  • For correspondence: fabian.theis@helmholtz-muenchen.de herbert.schiller@helmholtz-muenchen.de
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Abstract

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

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Posted June 20, 2018.
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An atlas of the aging lung mapped by single cell transcriptomics and deep tissue proteomics
Ilias Angelidis, Lukas M. Simon, Isis E. Fernandez, Maximilian Strunz, Christoph H. Mayr, Flavia R. Greiffo, George Tsitsiridis, Elisabeth Graf, Tim-Matthias Strom, Oliver Eickelberg, Matthias Mann, Fabian J. Theis, Herbert B. Schiller
bioRxiv 351353; doi: https://doi.org/10.1101/351353
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An atlas of the aging lung mapped by single cell transcriptomics and deep tissue proteomics
Ilias Angelidis, Lukas M. Simon, Isis E. Fernandez, Maximilian Strunz, Christoph H. Mayr, Flavia R. Greiffo, George Tsitsiridis, Elisabeth Graf, Tim-Matthias Strom, Oliver Eickelberg, Matthias Mann, Fabian J. Theis, Herbert B. Schiller
bioRxiv 351353; doi: https://doi.org/10.1101/351353

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