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

A single-cell approach

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, are leading causes 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 how to prevent or treat this. 

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

Uncovering new disease links

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.  

“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,” explained Elo Madissoon, Post-Doctoral Fellow at EMBL-EBI and the Wellcome Sanger Institute. “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.”

“Our freely available comprehensive lung atlas not only genetically profiles 80 cell types, including 11 new ones, it starts to describe how these communicate with each other,” said Kerstin Meyer, Principal Staff Scientist at the Wellcome Sanger Institute. “Our research builds on the single cell era and by including spatial data, we have begun to see how lung cells interact in their specific microenvironments. Understanding how lung cells interact with each other in a healthy lung is crucial if we hope to identify where something has gone wrong to cause disease. Our atlas is a valuable resource for the scientific community and we look forward to larger studies that will continue to piece together the full puzzle of how the lung works at a cellular level.” 

The original press release was published on the Sanger Institute website.

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