Plate IV.321 · Publications
Alterations of multiple alveolar macrophage states in chronic obstructive pulmonary disease
Preprint in bioRxiv, 30 May 2020.
Abstract
Despite the epidemics of chronic obstructive pulmonary disease (COPD), the cellular and molecular mechanisms of this disease are far from being understood. Here, we characterize and classify the cellular composition within the alveolar space and peripheral blood of COPD patients and control donors using a clinically applicable single-cell RNA-seq technology corroborated by advanced computational approaches for: machine learning-based cell-type classification, identification of differentially expressed genes, prediction of metabolic changes, and modeling of cellular trajectories within a patient cohort. These high-resolution approaches revealed: massive transcriptional plasticity of macrophages in the alveolar space with increased levels of invading and proliferating cells, loss of MHC expression, reduced cellular motility, altered lipid metabolism, and a metabolic shift reminiscent of mitochondrial dysfunction in COPD patients. Collectively, single-cell omics of multi-tissue samples was used to build the first cellular and molecular framework for COPD pathophysiology as a prerequisite to develop molecular biomarkers and causal therapies against this deadly disease.
Cite
@misc{bassler2020alterations,
title = {{Alterations of multiple alveolar macrophage states in chronic obstructive pulmonary disease}},
author = {Baßler, Kevin and Fujii, Wataru and Kapellos, Theodore S. and Horne, Arik and Reiz, Benedikt and Dudkin, Erika and Lücken, Malte and Reusch, Nico and Osei-Sarpong, Collins and Warnat-Herresthal, Stefanie and Wagner, Allon and Bonaguro, Lorenzo and Günther, Patrick and Pizarro, Carmen and Schreiber, Tina and Becker, Matthias and Händler, Kristian and Wohnhaas, Christian T. and Baumgartner, Florian and Köhler, Meike and Theis, Heidi and Kraut, Michael and Wadsworth, Marc H. and Hughes, Travis K. and Ferreira, Humberto J. G. and Schulte-Schrepping, Jonas and Hinkley, Emily and Kaltheuner, Ines H. and Geyer, Matthias and Thiele, Christoph and Shalek, Alex K. and Feißt, Andreas and Thomas, Daniel and Dickten, Henning and Beyer, Marc and Baum, Patrick and Yosef, Nir and Aschenbrenner, Anna C. and Ulas, Thomas and Hasenauer, Jan and Theis, Fabian J. and Skowasch, Dirk and Schultze, Joachim L.},
howpublished = {bioRxiv},
publisher = {openRxiv},
year = {2020},
month = may,
doi = {10.1101/2020.05.28.121541},
url = {https://doi.org/10.1101/2020.05.28.121541},
note = {Preprint}
}