Plate IV.198 · Publications
An integrated cell atlas of the lung in health and disease
Article in Nature Medicine, June 2023.
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.
Versions3
- PublishedNature Medicine10.1038/s41591-023-02327-2
- PreprintResearch Square10.21203/rs.3.rs-1438584/v1
- PreprintbioRxiv10.1101/2022.03.10.483747
Cite
@article{sikkema2023integrated,
title = {{An integrated cell atlas of the lung in health and disease}},
author = {Sikkema, Lisa and Ramírez-Suástegui, Ciro and Strobl, Daniel C. and Gillett, Tessa E. and Zappia, Luke and Madissoon, Elo and Markov, Nikolay S. and Zaragosi, Laure-Emmanuelle and Ji, Yuge and Ansari, Meshal and Arguel, Marie-Jeanne and Apperloo, Leonie and Banchero, Martin and Bécavin, Christophe and Berg, Marijn and Chichelnitskiy, Evgeny and Chung, Mei-i and Collin, Antoine and Gay, Aurore C. A. and Gote-Schniering, Janine and Hooshiar Kashani, Baharak and Inecik, Kemal and Jain, Manu and Kapellos, Theodore S. and Kole, Tessa M. and Leroy, Sylvie and Mayr, Christoph H. and Oliver, Amanda J. and von Papen, Michael and Peter, Lance and Taylor, Chase J. and Walzthoeni, Thomas and Xu, Chuan and Bui, Linh T. and De Donno, Carlo and Dony, Leander and Faiz, Alen and Guo, Minzhe and Gutierrez, Austin J. and Heumos, Lukas and Huang, Ni and Ibarra, Ignacio L. and Jackson, Nathan D. and Kadur Lakshminarasimha Murthy, Preetish and Lotfollahi, Mohammad and Tabib, Tracy and Talavera-López, Carlos and Travaglini, Kyle J. and Wilbrey-Clark, Anna and Worlock, Kaylee B. and Yoshida, Masahiro and Lung Biological Network Consortium and Chen, Yuexin and Hagood, James S. and Agami, Ahmed and Horvath, Peter and Lundeberg, Joakim and Marquette, Charles-Hugo and Pryhuber, Gloria and Samakovlis, Chistos and Sun, Xin and Ware, Lorraine B. and Zhang, Kun and van den Berge, Maarten and Bossé, Yohan and Desai, Tushar J. and Eickelberg, Oliver and Kaminski, Naftali and Krasnow, Mark A. and Lafyatis, Robert and Nikolic, Marko Z. and Powell, Joseph E. and Rajagopal, Jayaraj and Rojas, Mauricio and Rozenblatt-Rosen, Orit and Seibold, Max A. and Sheppard, Dean and Shepherd, Douglas P. and Sin, Don D. and Timens, Wim and Tsankov, Alexander M. and Whitsett, Jeffrey and Xu, Yan and Banovich, Nicholas E. and Barbry, Pascal and Duong, Thu Elizabeth and Falk, Christine S. and Meyer, Kerstin B. and Kropski, Jonathan A. and Pe’er, Dana and Schiller, Herbert B. and Tata, Purushothama Rao and Schultze, Joachim L. and Teichmann, Sara A. and Misharin, Alexander V. and Nawijn, Martijn C. and Luecken, Malte D. and Theis, Fabian J.},
journal = {Nature Medicine},
publisher = {Springer Science and Business Media LLC},
year = {2023},
month = jun,
doi = {10.1038/s41591-023-02327-2},
url = {https://doi.org/10.1038/s41591-023-02327-2},
pmid = {37291214},
pmcid = {PMC10287567}
}