@article{3526, keywords = {COVID-19, Humans, Lung, Lung Neoplasms, Macrophages, Pulmonary Fibrosis}, author = {Lisa Sikkema and Ciro Ramírez-Suástegui and Daniel C. Strobl and Tessa E. Gillett and Luke Zappia and Elo Madissoon and Nikolay S. Markov and Laure-Emmanuelle Zaragosi and Yuge Ji and Meshal Ansari and Marie-Jeanne Arguel and Leonie Apperloo and Martin Banchero and Christophe Bécavin and Marijn Berg and Evgeny Chichelnitskiy and Mei-I. Chung and Antoine Collin and Aurore C. A. Gay and Janine Gote-Schniering and Baharak Hooshiar Kashani and Kemal Inecik and Manu Jain and Theodore S. Kapellos and Tessa M. Kole and Sylvie Leroy and Christoph H. Mayr and Amanda J. Oliver and Michael von Papen and Lance Peter and Chase J. Taylor and Thomas Walzthoeni and Chuan Xu and Linh T. Bui and Carlo De Donno and Leander Dony and Alen Faiz and Minzhe Guo and Austin J. Gutierrez and Lukas Heumos and Ni Huang and Ignacio L. Ibarra and Nathan D. Jackson and Preetish Kadur Lakshminarasimha Murthy and Mohammad Lotfollahi and Tracy Tabib and Carlos Talavera-López and Kyle J. Travaglini and Anna Wilbrey-Clark and Kaylee B. Worlock and Masahiro Yoshida and Lung Biological Network Consortium and Maarten van den Berge and Yohan Bossé and Tushar J. Desai and Oliver Eickelberg and Naftali Kaminski and Mark A. Krasnow and Robert Lafyatis and Marko Z. Nikolić and Joseph E. Powell and Jayaraj Rajagopal and Mauricio Rojas and Orit Rozenblatt-Rosen and Max A. Seibold and Dean Sheppard and Douglas P. Shepherd and Don D. Sin and Wim Timens and Alexander M. Tsankov and Jeffrey Whitsett and Yan Xu and Nicholas E. Banovich and Pascal Barbry and Thu Elizabeth Duong and Christine S. Falk and Kerstin B. Meyer and Jonathan A. Kropski and Dana Pe'er and Herbert B. Schiller and Purushothama Rao Tata and Joachim L. Schultze and Sara A. Teichmann and Alexander V. Misharin and Martijn C. Nawijn and Malte D. Luecken and Fabian J. Theis}, title = {An integrated cell atlas of the lung in health and disease}, abstract = {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.}, year = {2023}, journal = {Nature Medicine}, volume = {29}, pages = {1563-1577}, month = {2023-06}, issn = {1546-170X}, doi = {10.1038/s41591-023-02327-2}, language = {eng}, }