TY - JOUR AU - Sikkema, Lisa AU - Ramírez-Suástegui, Ciro AU - Strobl, Daniel C AU - Gillett, Tessa E AU - Zappia, Luke AU - Madissoon, Elo AU - Markov, Nikolay S AU - Zaragosi, Laure-Emmanuelle AU - Ji, Yuge AU - Ansari, Meshal AU - Arguel, Marie-Jeanne AU - Apperloo, Leonie AU - Banchero, Martin AU - Bécavin, Christophe AU - Berg, Marijn AU - Chichelnitskiy, Evgeny AU - Chung, Mei-I AU - Collin, Antoine AU - Gay, Aurore C A AU - Gote-Schniering, Janine AU - Hooshiar Kashani, Baharak AU - Inecik, Kemal AU - Jain, Manu AU - Kapellos, Theodore S AU - Kole, Tessa M AU - Leroy, Sylvie AU - Mayr, Christoph H AU - Oliver, Amanda J AU - von Papen, Michael AU - Peter, Lance AU - Taylor, Chase J AU - Walzthoeni, Thomas AU - Xu, Chuan AU - Bui, Linh T AU - De Donno, Carlo AU - Dony, Leander AU - Faiz, Alen AU - Guo, Minzhe AU - Gutierrez, Austin J AU - Heumos, Lukas AU - Huang, Ni AU - Ibarra, Ignacio L AU - Jackson, Nathan D AU - Kadur Lakshminarasimha Murthy, Preetish AU - Lotfollahi, Mohammad AU - Tabib, Tracy AU - Talavera-López, Carlos AU - Travaglini, Kyle J AU - Wilbrey-Clark, Anna AU - Worlock, Kaylee B AU - Yoshida, Masahiro AU - van den Berge, Maarten AU - Bossé, Yohan AU - Desai, Tushar J AU - Eickelberg, Oliver AU - Kaminski, Naftali AU - Krasnow, Mark A AU - Lafyatis, Robert AU - Nikolic, Marko Z AU - Powell, Joseph E AU - Rajagopal, Jayaraj AU - Rojas, Mauricio AU - Rozenblatt-Rosen, Orit AU - Seibold, Max A AU - Sheppard, Dean AU - Shepherd, Douglas P AU - Sin, Don D AU - Timens, Wim AU - Tsankov, Alexander M AU - Whitsett, Jeffrey AU - Xu, Yan AU - Banovich, Nicholas E AU - Barbry, Pascal AU - Duong, Thu Elizabeth AU - Falk, Christine S AU - Meyer, Kerstin B AU - Kropski, Jonathan A AU - Pe'er, Dana AU - Schiller, Herbert B AU - Tata, Purushothama Rao AU - Schultze, Joachim L AU - Teichmann, Sara A AU - Misharin, Alexander V AU - Nawijn, Martijn C AU - Luecken, Malte D AU - Theis, Fabian J TI - An integrated cell atlas of the lung in health and disease. JO - Nature medicine VL - 29 IS - 6 SN - 1078-8956 CY - New York, NY PB - Nature America Inc. M1 - DZNE-2023-00690 SP - 1563 - 1577 PY - 2023 AB - Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations of individual studies and capture the variability present in the population. Here we present the integrated Human Lung Cell Atlas (HLCA), combining 49 datasets of the human respiratory system into a single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents a consensus cell type re-annotation with matching marker genes, including annotations of rare and previously undescribed cell types. Leveraging the number and diversity of individuals in the HLCA, we identify gene modules that are associated with demographic covariates such as age, sex and body mass index, as well as gene modules changing expression along the proximal-to-distal axis of the bronchial tree. Mapping new data to the HLCA enables rapid data annotation and interpretation. Using the HLCA as a reference for the study of disease, we identify shared cell states across multiple lung diseases, including SPP1+ profibrotic monocyte-derived macrophages in COVID-19, pulmonary fibrosis and lung carcinoma. Overall, the HLCA serves as an example for the development and use of large-scale, cross-dataset organ atlases within the Human Cell Atlas. KW - Humans KW - COVID-19 KW - Lung KW - Pulmonary Fibrosis KW - Lung Neoplasms: genetics KW - Macrophages LB - PUB:(DE-HGF)16 C6 - pmid:37291214 C2 - pmc:PMC10287567 DO - DOI:10.1038/s41591-023-02327-2 UR - https://pub.dzne.de/record/258918 ER -