Spatial lung cell atlas offers insights into disease and immune function

The most comprehensive lung cell atlas to date, from the Wellcome Sanger Institute, UK, and collaborators, has revealed 11 new lung cell types and offers detailed insight into an immune process involved in fighting lung infections.

Published in Nature Genetics, this freely available resource highlights multiple immune cells, barrier cells, and their environments in the lung that are implicated in respiratory diseases and infections.

This new lung cell atlas, which is part of the wider international Human Cell Atlas Initiative, combined single cell sequencing with spatial transcriptomics to provide a fuller picture of how cells interact and communicate with each other.

While single cell studies have advanced the understanding of lung function, the lungs are made up of complex structures and environments that cannot be investigated by single cell sequencing alone. For example, there are many unanswered questions about how the cells are organised and how specific cell types, especially rare cell types, contribute to lung disease.

Chronic lung diseases, such as chronic obstructive pulmonary disease (COPD) and interstitial lung disease. According to the World Health Organization, COPD is the third leading cause of death worldwide. Understanding communication between cells within their local environment in healthy lungs can help determine what is disrupted in disease and give clues on how to prevent or treat this.

In this study, researchers from the Wellcome Sanger Institute and collaborators, genetically profiled nearly 200,000 cells from lung tissue of 13 donors, discovering 11 new cell types, and showing the exact location of 80 cell types in total.

Of these new cell types, peribronchial fibroblasts were found to be implicated in COPD and idiopathic pulmonary fibrosis. While further research is required to investigate how these cells are involved, this discovery demonstrates the potential of using this lung atlas to uncover new links between cell pathways and disease. 

Dr Elo Madissoon, joint first author and Post-Doctoral Fellow at the Wellcome Sanger Institute and EMBL’s European Bioinformatics Institute (EMBL-EBI), said: “By being able to analyse multiple locations of the same lung, we were able to get key information about a range of cells in a single study, many of which were not previously mapped. In addition, the link we found between peribronchial fibroblasts and chronic lung conditions shows how this atlas goes beyond reference data and can offer new insights into disease.”

In addition to this, the researchers were able to define a lung microenvironment which they call the gland associated immune niche (GAIN). The GAIN exists to help fight respiratory infections and ultimately promotes IgA antibody production. This is the first time research has managed to map this complex process in detail.

IgA responses are important for efficient protection against respiratory infections and are impaired in lung diseases, such as COPD and cystic fibrosis. Further research investigating GAIN function could help develop therapies to alleviate disease symptoms, improve resistance to infection or create ways to boost vaccine responses.