Human Lung Cell Atlas published – and offers unparalleled cellular insight into organ

The Human Lung Cell Atlas has been unveiled and is expected to be a hugely valuable resource for researchers.

The largest and most comprehensive cellular map of the human lung was created by combining 49 datasets from nearly 40 studies using advanced machine learning.

The first integrated single-cell atlas of the lung, it reveals rare cell types and highlights cellular differences between healthy people.

Common cell states between lung fibrosis, cancer and Covid-19 were uncovered in its creation, suggesting new ways of understanding lung disease that could aid the hunt for therapies.

Spanning 2.4 million cells from 486 individuals, the study, published in Nature Medicine, is part of the global Human Cell Atlas (HCA) initiative to map every cell type in the human body, which was co-founded by Dr Sarah Teichmann at the Wellcome Sanger Institute at Hinxton.

Senior author Prof Fabian Theis, director of the Institute of Computational Biology at Helmholtz Munich, said: “We have created a first reference atlas of the human lung, which includes data from more than 100 healthy people and reveals how the cells from individuals vary with age, sex, and smoking history. The sheer numbers of cells and individuals involved now gives the power to see rare cell types and identify new cell states that have not previously been described.”

The team also took datasets from more than 10 different lung diseases and projected these onto the healthy data to understand the differences.

Among the findings was that a subset of macrophages – a type of immune cell – share similar gene activity in lung fibrosis, cancer and Covid, indicating these cells could play a similar role in scar formation in the lung in all three diseases.

Prof Martijn Nawijn, a senior author on the paper and professor at the University Medical Center 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 Malte Luecken, a senior author on the paper and group leader at the Institute of Computational Biology and the Institute of Lung Health and Immunity at 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.”

Nearly 100 partners from 60 departments were involved in the study, which meant the team had to work out a method of standardising annotation of different cell types.

Lisa Sikkema, the first author on the paper and PhD student at the Institute of Computational Biology at Helmholtz Munich, explained: “One of the big problems in creating the integrated lung cell atlas was with cell type annotation. Different research groups used different names for the same cell type, or the same name for different cells, so as a team we worked to standardise them using the data in the atlas.

“The atlas is a first step towards a consensus annotation of the human lung, which will help bring together the field of lung research.”

Dr Alexander Misharin, a senior author on the paper and Associate Professor at Northwestern University Feinberg School of Medicine, USA, 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”.