The Wellcome Sanger Institute and collaborators report they have developed a lung cell atlas that reveals 11 new lung cell types and provides new insights into an immune process involved in fighting lung infections.

Their findings, “A spatially resolved atlas of the human lung characterizes a gland-associated immune niche,” are published in Nature Genetics and highlight multiple immune cells, barrier cells, and their environments in the lung that are implicated in respiratory diseases and infections.

“Single-cell transcriptomics has allowed unprecedented resolution of cell types/states in the human lung, but their spatial context is less well defined,” wrote the researchers. “To (re)define tissue architecture of lung and airways, we profiled five proximal-to-distal locations of healthy human lungs in depth using multi-omic single cell/nuclei and spatial transcriptomics (queryable at lungcellatlas.org). Using computational data integration and analysis, we extend beyond the suspension cell paradigm and discover macro- and micro-anatomical tissue compartments including previously unannotated cell types in the epithelial, vascular, stromal, and nerve bundle micro-environments.”

The 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.

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

Of the new cell types, peribronchial fibroblasts were found to be implicated in COPD and idiopathic pulmonary fibrosis.

Further research is required to observe how these cells are involved, yet discovery demonstrates the potential of using the lung atlas to uncover new links between cell pathways and disease.

“By being able to analyze 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, PhD, joint first author and postdoctoral fellow at the Wellcome Sanger Institute and EMBL’s European Bioinformatics Institute (EMBL-EBI).

“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.”

The researchers were also able to define a lung microenvironment which they call the gland-associated immune niche (GAIN).

“Our study provides unique information about how cells communicate in the human lung and airways,” said Amanda Oliver, PhD, joint first author and postdoctoral research fellow at the Wellcome Sanger Institute. “By integrating single cell and spatial data, we were able to study how epithelial, endothelial, and immune cells interact to form an immune niche— the GAIN—which is likely to be important for protection against respiratory infections. Our single-cell data allows us to drill into the signaling circuits that enable this immune niche to function and could be crucial in developing new ways to treat disease in the future.”

The atlas provides a detailed understanding of cells and may explain many aspects of human health and disease. Their findings could help identify which pathways or cells in the lung could be targeted to help improve immunity in individuals with impaired lung function.