< At-a-Glance Summaries
Date of Publication:
24th September 2025
Scientists have mapped underappreciated scaffolding cells in skin, known as fibroblasts. They show for the first time how fibroblasts go ‘rogue’ in many different diseases affecting multiple organs – from acne and psoriasis, to rheumatoid arthritis and inflammatory bowel disease.
Researchers at the Wellcome Sanger Institute, the Universities of Cambridge and Newcastle, and their collaborators combined single-cell sequencing and spatial genomics datasets with machine learning to identify eight different types of fibroblasts. They show how the fibroblasts form distinct ‘tissue neighbourhoods’ in skin and reveal their shared functions in a range of diseases across various tissues.
Published in Nature Immunology, the researchers suggest that fibroblasts show potential as universal drug targets due to their involvement in multiple diseases across a range of tissues.
This study is part of the international Human Cell Atlas (HCA) consortium, which is mapping all human cells to understand human health, and help diagnose, monitor, and treat disease.
Skin is the largest organ in the body and plays an essential role in protecting us from infections. Two in three British people will suffer from skin disease at some point in their lifetime. Skin diseases account for 24 per cent of the UK’s burden of illness, with wound care costing the NHS approximately £8.3 billion annually, and other skin conditions and diseases costing approximately £723 million each year.
Scaffolding cells, known as fibroblasts, are found in skin and every other organ in the body. They are involved in wound healing, scarring, tissue repair, the development of connective tissues and maintenance of skin.
Until now, skin fibroblasts have been somewhat overlooked, partly because their diversity has been difficult to study. While it is known that fibroblasts increase their collagen production and develop muscle-like fibres to contract after wounding, it has been unclear how fibroblast states change across the many diseases observed in skin, from cancers to acne.
Understanding the true diversity of fibroblasts and where they are located in tissues, in both health and disease, presents enormous clinical opportunities due to their roles in scarring and inflammation.
In a new study, Sanger Institute researchers and their collaborators set out to map fibroblasts in human skin, from healthy skin samples and 23 skin disorders, including psoriasis, lupus, skin cancers and acne.
The team generated spatial transcriptomic data – which measures gene expression and how it varies across different locations within a tissue – to spatially map the identified fibroblast populations from normal and diseased human skin.
The researchers found that these scaffolding cells are far more complex than was previously thought. The team discovered five different types of fibroblasts in healthy skin, which are located in distinct ‘tissue neighbourhoods’ associated with specific functions. Following this, the team looked at fibroblasts and their ‘tissue neighbourhoods’ in many other organs, including the endometrium, gut and lung in 14 diseases, such as inflammatory bowel disease and lung cancer. The team identified fibroblast populations shared across organs.
Using machine learning models, they identified three ‘rogue’ subtypes of fibroblasts that are present in different organs across multiple diseases, including scarring diseases and lung cancer, rheumatoid arthritis in joints and inflammatory bowel disease in the gut.
Interestingly, the researchers found that the same activated fibroblasts that recruit immune cells to early skin wounds were observed in inflammatory diseases, such as acne and inflammatory bowel disease. This suggests that a wound-like fibroblast state is used to attract immune cells to tissues in diseases like acne and inflammatory bowel disease, which both have a risk of scarring.
By identifying shared disease-related and disease-specific fibroblasts within these ‘tissue neighbourhoods’ across multiple diseases and organs, the researchers identify potential universal drug targets. This means researchers may be able to develop single drugs that work for several diseases across the body.
In the future, the team aims to extend this research to many other cell types across all of the tissues in the human body, and use machine learning and artificial intelligence to find disease-specific ‘tissue neighbourhoods’ that can be modulated for therapy.
For more details, you can read the original Wellcome Sanger press release, and the full paper is available to read online here: https://doi.org/10.1038/s41590-025-02267-8. The research was supported by Wellcome. For full funding information, please refer to the publication.
Authors:
Steele L, Olabi B, Roberts K, et al.
Journal:
Nature Immunology
Link:
< At-a-Glance Summaries