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; Meshal Ansari; Elisabeth Graf; Tim-Matthias Strom; Monica Nagendran; Tushar Desai; Oliver Eickelberg; Matthias Mann; Fabian J Theis; Herbert B Schiller

doi:10.1038/s41467-019-08831-9

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, Meshal Ansari, Elisabeth Graf, Tim-Matthias Strom, Monica Nagendran, Tushar Desai, Oliver Eickelberg, Matthias Mann, Fabian J Theis, Herbert B Schiller

96 Citations (Scopus)

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.

Original language	English
Journal	Nature Communications
Volume	10
Issue number	1
Pages (from-to)	963
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-019-08831-9
Publication status	Published - 1 Dec 2019
Externally published	Yes

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Angelidis, I., Simon, L. M., Fernandez, I. E., Strunz, M., Mayr, C. H., 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. (2019). An atlas of the aging lung mapped by single cell transcriptomics and deep tissue proteomics. Nature Communications, 10(1), 963. https://doi.org/10.1038/s41467-019-08831-9

Angelidis, I, Simon, LM, Fernandez, IE, Strunz, M, Mayr, CH, Greiffo, FR, Tsitsiridis, G, Ansari, M, Graf, E, Strom, T-M, Nagendran, M, Desai, T, Eickelberg, O, Mann, M, Theis, FJ & Schiller, HB 2019, 'An atlas of the aging lung mapped by single cell transcriptomics and deep tissue proteomics', Nature Communications, vol. 10, no. 1, pp. 963. https://doi.org/10.1038/s41467-019-08831-9

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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. 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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AU - Mayr, Christoph H

AU - Greiffo, Flavia R

AU - Tsitsiridis, George

AU - Ansari, Meshal

AU - Graf, Elisabeth

AU - Strom, Tim-Matthias

AU - Nagendran, Monica

AU - Desai, Tushar

AU - Eickelberg, Oliver

AU - Mann, Matthias

AU - Theis, Fabian J

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N2 - 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.

AB - 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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JO - Nature Communications

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

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