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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 01, 2023
- Source ID
- 10.1038/s41591-023-02327-2
Entities
People
- Ahmed Agami
- Alen Faiz
- Alexander M. Tsankov
- Alexander V. Misharin
- Amanda J. Oliver
- Anna Wilbrey-clark
- Antoine Collin
- Aurore Gay
- Austin J. Gutierrez
- Baharak Hooshiar Kashani
- Carlo De Donno
- Carlos Talavera-lópez
- Charles-hugo Marquette
- Chase J. Taylor
- Chistos Samakovlis
- Christine S. Falk
- Christoph H. Mayr
- Christophe Bécavin
- Chuan Xu
- Ciro Ramírez-suástegui
- Dana Pe'er
- Daniel C. Strobl
- Dean Sheppard
- Don D Sin
- Douglas P. Shepherd
- Elo Madissoon
- Evgeny Chichelnitskiy
- Fabian J. Theis
- Gloria S Pryhuber
- Herbert B Schiller
- Ignacio Ibarra
- James S. Hagood
- Janine Gote-schniering
- Jayaraj Rajagopal
- Jeffrey A Whitsett
- Joachim L. Schultze
- Joakim Lundeberg
- Jonathan Andrew Kropski
- Joseph E. Powell
- Kaylee Worlock
- Kemal İnecik
- Kerstin B Meyer
- Kun Zhang
- Kyle Travaglini
- Lance Peter
- Laure-Emmanuelle Zaragosi
- Leander Dony
- Leonie Apperloo
- Linh T Bui
- Lisa Sikkema
- Lorraine B Ware
- Lukas Heumos
- Luke Zappia
- Lung Biological Network Consortium
- Maarten Van Den Berge
- Malte D Luecken
- Manu Jain
- Marie-Jeanne Arguel
- Marijn Berg
- Mark A Krasnow
- Marko Z Nikolic
- Martijn C Nawijn
- Martin Banchero
- Masahiro Yoshida
- Mauricio Rojas
- Max A Seibold
- Mei-i Chung
- Meshal Ansari
- Michael von Papen
- Minzhe Guo
- Mohammad Lotfollahi
- Naftali Kaminski
- Nathan D. Jackson
- Ni Huang
- Nicholas E Banovich
- Nikolay S Markov
- Oliver Eickelberg
- Orit Rozenblatt-Rosen
- Pascal Barbry
- Peter Horvath
- Preetish Kadur Lakshminarasimha Murthy
- Purushothama Rao Tata
- Robert Lafyatis
- Sarah Teichmann
- Sylvie Leroy
- Tessa E. Gillett
- Tessa M. Kole
- Theodore S. Kapellos
- Thomas Walzthoeni
- Thu Duong
- Tracy Tabib
- Tushar J Desai
- Wim Timens
- Xin Sun
- Yan Xu
- Yohan Bossé
- Yuexin Chen
- Yuge Ji