An integrated cell atlas of the lung in health and disease

Researchers have created an atlas that provides a detailed representation of the composition of the human lung in various cell types for the first time. This map reveals the extensive diversity of cells in the lung and unveils both significant differences between diseased and healthy lungs, as well as similarities between different diseases. With the so-called "Human Lung Cell Atlas," researchers and doctors can now better understand and treat lung diseases.

The results of this research are published today in the scientific journal Nature Medicine. Researcher Martijn Nawijn leads this study at UMCG and has been working for years on mapping the lung. "In this atlas, we have combined all the data from available scientific studies on the cell composition of the lung using artificial intelligence, creating a single dataset. This allows us to compare which cells are present in the healthy lung, how they change in different diseases, and identify similarities between the diseases." 

Three diseases, one macrophage

Using this map, the researchers discovered, for example,  a particular type of macrophage, which is absent in healthy lungs but present in the lungs of patients with lung fibrosis, lung cancer, and COVID-19. All three diseases involve a fibrotic disease process, meaning that scar tissue forms in the lung. Macrophages clear pathogens in the body but leave behind scar tissue. This causes significant problems in the lung as scar tissue is stiff and hampers gas exchange necessary for breathing. Nawijn states: ‘The discovery that one type of cell is involved in these different diseases reveals a completely different way of looking at lung diseases, which offers possibilities for new treatments. Our findings also suggest that therapies effective for one disease may potentially alleviate other diseases as well.’

40 studies in one dataset using machine learning

The lung atlas contains 2.4 million cells from 486 different individuals. The researchers first created a map of the healthy lung using data on the cell composition of lung tissue from over 100 healthy donors in 14 different studies. The cells were carefully characterized, revealing differences even among the same cells in different locations within the lung. They also observed variation between the same cells in the lungs of young and old donors. After creating the lung atlas, the researchers added data from more than 375 lungs, both from healthy individuals and patients with lung diseases such as COVID-19, COPD, lung fibrosis, and lung cancer. Nawijn explains: ‘This makes it possible to meticulously map and compare changes in cells in a diseased lung, providing great detail, and allows for comparisons between different diseases.’

Significant potential

Nawijn believes that the lung atlas can be valuable to many people. ‘Researchers can use it to compare the effects of different diseases on the lung, study the effects of aging, and map markers to monitor the disease process.’ He also aims to make the atlas accessible to patients: ‘In this way, we hope that patients will better understand what is happening with their disease and be able to discuss it with their doctors.’ Nawijn and his colleagues are already working on a next version of the atlas: ‘We eventually aim to create a reference map that doctors can use to quickly map the disease and its underlying mechanisms by comparing a patient's sample. This would allow doctors to treat patients much faster and more specifically with treatments tailored to the individual patient.’

International collaboration

The lung atlas was created through a large international collaboration of researchers from over 40 institutes worldwide and was coordinated by researchers from the University Medical Center Groningen, the Helmholtz Munich research center, and Northwestern University Feinberg School of Medicine in Chicago.

The Human Cell Atlas

The lung atlas is part of a larger project called "The Human Cell Atlas”,  in which researchers aim to map every cell in the human body. The goal is to gain a better understanding of human health and the development, progression, and treatment of diseases. This international collaboration was established in 2016 by researchers Sarah Teichmann of the Wellcome Sanger Institute (United Kingdom) and Aviv Regev then at the Broad Institute of MIT and Harvard (USA). Currently, more than 2,900 researchers from 94 countries are working together on this project.