An integrated cell atlas of the lung in health and disease
Authors: Sikkema Lisa , Ramírez-Suástegui Ciro , Strobl Daniel C. , Gillett Tessa E. , Zappia Luke , Madissoon Elo , Markov Nikolay S. , Zaragosi Laure-Emmanuelle , Ji Yuge , Ansari Meshal , Arguel Marie-Jeanne , Apperloo Leonie , Banchero Martin , Bécavin Christophe , Berg Marijn , Chichelnitskiy Evgeny , Chung Mei-i , Collin Antoine , Gay Aurore C. A. , Gote-Schniering Janine , Hooshiar Kashani Baharak , Inecik Kemal , Jain Manu , Kapellos Theodore S. , Kole Tessa M. , Leroy Sylvie , Mayr Christoph H. , Oliver Amanda J. , von Papen Michael , Peter Lance , Taylor Chase J. , Walzthoeni Thomas , Xu Chuan , Bui Linh T. , De Donno Carlo , Dony Leander , Faiz Alen , Guo Minzhe , Gutierrez Austin J. , Heumos Lukas , Huang Ni , Ibarra Ignacio L. , Jackson Nathan D. , Kadur Lakshminarasimha Murthy Preetish , Lotfollahi Mohammad , Tabib Tracy , Talavera-López Carlos , Travaglini Kyle J. , Wilbrey-Clark Anna , Worlock Kaylee B. , Yoshida Masahiro ,   Lung Biological Network Consortium, Chen Yuexin , Hagood James S. , Agami Ahmed , Horvath Peter , Lundeberg Joakim , Marquette Charles-Hugo , Pryhuber Gloria , Samakovlis Chistos , Sun Xin , Ware Lorraine B. , Zhang Kun , van den Berge Maarten , Bossé Yohan , Desai Tushar J. , Eickelberg Oliver , Kaminski Naftali , Krasnow Mark A. , Lafyatis Robert , Nikolic Marko Z. , Powell Joseph E. , Rajagopal Jayaraj , Rojas Mauricio , Rozenblatt-Rosen Orit , Seibold Max A. , Sheppard Dean , Shepherd Douglas P. , Sin Don D. , Timens Wim , Tsankov Alexander M. , Whitsett Jeffrey , Xu Yan , Banovich Nicholas E. , Barbry Pascal , Duong Thu Elizabeth , Falk Christine S. , Meyer Kerstin B. , Kropski Jonathan A. , Pe’er Dana , Schiller Herbert B. , Tata Purushothama Rao , Schultze Joachim L. , Teichmann Sara A. , Misharin Alexander V. , Nawijn Martijn C. , Luecken Malte D. , Theis Fabian J. 
Published: June 2023

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.