The largest and most comprehensive cell map of the human lung has been published for the first time, providing valuable insight into lung diseases.
The cell map, announced in Nature Medicine combines data from nearly 40 studies and is the first integrated single-cell atlas of the lung, revealing rare cell types and highlighting cellular differences between healthy people.
The project, part of the global Human Cell Atlas (HCA) initiative to map every cell type in the human body, was an international collaborative effort with nearly 100 partners from more than 60 departments, including key researchers from Helmholtz Munich, Germany; University Medical Center Groningen, the Netherlands; and Northwestern University, USA.
The study found common cell states between lung fibrosis, cancer and COVID-19, offering new ways of understanding lung disease, which could help identify new therapeutic targets.
The team successfully combined 49 lung datasets, from nearly 40 separate studies, into a single integrated atlas, using advanced machine learning. It spans more than 2.4 million cells from 486 individuals and gives new insights into lung biology that were previously not possible.
Senior author Dr Malte Luecken, from Helmholtz Munich, Germany, said: “A comprehensive organ atlas requires many datasets to capture the diversity between both cells and individuals, but combining different datasets is a huge challenge.
“We developed a benchmarking pipeline to find the optimal method to integrate all datasets into the Atlas, using artificial intelligence, and successfully combined knowledge and data from almost 40 previous lung studies.”
While the core of the Human Lung Cell Atlas is data from healthy lungs, the team also took datasets from more than 10 different lung diseases and projected these onto the healthy data, to understand disease states.
They found different lung diseases shared common immune cell states, including that a subset of macrophages shared similar gene activity in lung fibrosis, cancer and Covid-19.
Senior author Professor Martijn Nawijn, of the University Medical Centre Groningen, the Netherlands, said: “This is the first effort to compare healthy and diseased lungs in one study in an integrated way.
“Our study not only supports the presence of lung fibrosis in Covid-19, it allows us to identify and define a shared cell state between lung fibrosis, Covid-19 and lung cancer patients.
“Finding these shared disease-associated cells is really exciting and reveals a totally different way of looking at lung diseases, opening possibilities for novel treatment targets and developing treatment response biomarkers. Our findings also suggest that therapies working for one disease may help alleviate others.”
Dr Alexander Misharin, a senior author and associate professor at Northwestern University Feinberg School of Medicine, added: “The Human Lung Cell Atlas is a huge resource for the scientific and medical community. Openly available to researchers, new disease data can be mapped onto the HLCA, transforming research into lung biology and disease. As the first whole reference atlas of a major organ, the HLCA also represents a milestone towards achieving a full Human Cell Atlas which will transform our understanding of biology and disease and lay the foundation for a new era of healthcare”.
Sikkema L et al. An integrated cell atlas of the lung in health and disease. Nature Medicine 8 June 2023; doi:10.1038/s41591-023-02327-2
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