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Plate IV.364 · Publications

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

Article in Nature Communications, 27 February 2019.

Open accessLung, Epithelial Cells

  1. Ilias Angelidis
  2. Lukas M. Simon
  3. Isis E. Fernandez
  4. Maximilian Strunz
  5. Christoph H. Mayr
  6. Flavia R. Greiffo
  7. George Tsitsiridis
  8. Meshal Ansari
  9. Elisabeth Graf
  10. Tim-Matthias Strom
  11. Monica Nagendran
  12. Tushar Desai
  13. Oliver Eickelberg
  14. Matthias Mann
  15. Fabian J. Theis
  16. Herbert 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.

Versions2

  1. PublishedNature Communications10.1038/s41467-019-08831-9
  2. PreprintbioRxiv10.1101/351353

Cite

@article{angelidis2019atlas,
  title = {{An atlas of the aging lung mapped by single cell transcriptomics and deep tissue proteomics}},
  author = {Angelidis, Ilias and Simon, Lukas M. and Fernandez, Isis E. and Strunz, Maximilian and Mayr, Christoph H. and Greiffo, Flavia R. and Tsitsiridis, George and Ansari, Meshal and Graf, Elisabeth and Strom, Tim-Matthias and Nagendran, Monica and Desai, Tushar and Eickelberg, Oliver and Mann, Matthias and Theis, Fabian J. and Schiller, Herbert B.},
  journal = {Nature Communications},
  publisher = {Springer Science and Business Media LLC},
  year = {2019},
  month = feb,
  doi = {10.1038/s41467-019-08831-9},
  url = {https://doi.org/10.1038/s41467-019-08831-9},
  pmid = {30814501},
  pmcid = {PMC6393476}
}
.bib file