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Developing a map of human lung fibrosis

Southampton researchers have given new insight into the events underlying a chronic lung disease, generating a valuable new resource for scientists around the world.

The study, published in Cell Reports, used a new technique called spatially resolved transcriptomics to generate a ‘map’ of human lung fibrosis tissue.

This offers unprecedented insight into how lung fibrosis may develop. It has also identified new pathways that may underlie susceptibility to disease progression.

Chronic lung disease

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease. Average life expectancy is just three to five years after diagnosis.

The condition causes scarring in the lungs and makes breathing increasingly difficult.

Treatment options are limited and researchers are intensely investigating how the disease progresses.

A significant challenge has been that the structure of lung tissue is very complex. Where different cell types are located within the lung and how they change with fibrosis has been poorly understood.

Spatial transcriptomics

The development of spatially resolved transcriptomics was Nature’s method of the year in 2020.

For the first time it allows assessment of gene expression signatures of cells within tissue without losing information about their physical location.

Collaborative research

The new study was driven by experts from the NIHR Southampton Biomedical Research Centre and the University of Southampton.

Dr Joseph Bell, NC3Rs Fellow in Southampton, performed the study in collaboration with the Medicines Discovery Catapult (MDC), Cheshire. It also included expertise from University College Dublin.

Dr Bell said: “Spatial transcriptomics has the potential to transform our understanding of complex diseases such as IPF. For the first time we have been able to identify all of the individual cell types within an area of lung tissue and understand how altered communication between each cell type may determine whether fibrosis develops.”

The work was led by Southampton’s Dr Mark Jones, Associate Professor in Respiratory Medicine and Honorary Consultant Respiratory Physician, who said:

“This has provided a unique snapshot of how lung fibrosis is developing. We see evidence of the very early events we think are underlying fibrosis development, as well as how the cellular environment may be promoting fibrosis progression.

“This will inform new ways to target lung fibrosis as well as how to create better models of lung disease to study these new treatments.”

Image: Visualised gene expression patterns within human lung fibrosis tissue.


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