1. An integrated cell atlas of the human lung in health and disease
- Author
-
Malte Luecken, Lisa Sikkema, Daniel Strobl, Luke Zappia, Elo Madissoon, Nikolay Markov, Laure-Emmanuelle Zaragosi, Meshal Ansari, Marie-Jeanne Arguel, Leonie Apperloo, Christophe Becavin, Marijn Berg, Evgeny Chichelnitskiy, Mei-i Chung, Antoine Collin, Aurore Gay, Baharak Hooshiar Kashani, Manu Jain, Theodore Kapellos, Tessa Kole, Christoph Mayr, Michael von Papen, Lance Peter, Ciro Ramírez-Suástegui, Janine Schniering, Chase Taylor, Thomas Walzthoeni, Chuan Xu, Linh Bui, Carlo de Donno, Leander Dony, Minzhe Guo, Austin Gutierrez, Lukas Heumos, Ni Huang, Ignacio Ibarra Del Río, Nathan Jackson, Preetish Kadur Lakshminarasimha Murthy, Mohammad Lotfollahi, Tracy Tabib, Carlos Talavera-Lopez, Kyle Travaglini, Anna Wilbrey-Clark, Kaylee Worlock, Masahiro Yoshida, Tushar Desai, Orit Rozenblatt-Rosen, Christine Falk, Naftali Kaminski, Mark Krasnow, Robert Lafyatis, Marko Nikolic, Joseph Powell, Jay Rajagopal, Max Seibold, Dean Sheppard, Douglas Shepherd, Sarah Teichmann, Alexander Tsankov, Jeffrey Whitsett, Yan Xu, Nicholas Banovich, Pascal Barbry, Thu Duong, Kerstin Meyer, Jonathan Kropski, Dana Pe'er, Herbert Schiller, Purushothama Rao Tata, Joachim Schultze, Maarten van den Berge, Yuexin Chen, James Hagood, Ahmed Hassan, Peter Horvath, Joakim Lundeberg, Sylvie Leroy, Charles Marquette, Gloria Pryhuber, Christos Samakovlis, Xin Sun, Lorraine Ware, Kun Zhang, Alexander Misharin, Martijn Nawijn, and Fabian Theis
- Abstract
Organ- and body-scale cell atlases have the potential to transform our understanding of human biology. To capture the variability present in the population, these atlases must include diverse demographics such as age and ethnicity from both healthy and diseased individuals. The growth in both size and number of single-cell datasets, combined with recent advances in computational techniques, for the first time makes it possible to generate such comprehensive large-scale atlases through integration of multiple datasets. Here, we present the integrated Human Lung Cell Atlas (HLCA) combining 46 datasets of the human respiratory system into a single atlas spanning over 2.2 million cells from 444 individuals across health and disease. The HLCA contains a consensus re-annotation of published and newly generated datasets, resolving under- or misannotation of 59% of cells in the original datasets. The HLCA enables recovery of rare cell types, provides consensus marker genes for each cell type, and uncovers gene modules associated with demographic covariates and anatomical location within the respiratory system. To facilitate the use of the HLCA as a reference for single-cell lung research and allow rapid analysis of new data, we provide an interactive web portal to project datasets onto the HLCA. Finally, we demonstrate the value of the HLCA reference for interpreting disease-associated changes. Thus, the HLCA outlines a roadmap for the development and use of organ-scale cell atlases within the Human Cell Atlas.
- Published
- 2022