Scientists have created a highly detailed map of skin, which reveals that cellular processes from development are re-activated in cells from patients with inflammatory skin disease.
The researchers from Newcastle University, the Wellcome Sanger Institute and Kings College London, discovered that skin from eczema and psoriasis patients share many of the same molecular pathways as developing skin cells. This offers potential new drug targets for treating these painful skin diseases.
Published in Science, the study also provides a completely new understanding of inflammatory disease, opening up new avenues for research on other inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease.
Discovering that developing cell pathways re-emerge is a huge leap in our understanding of inflammatory skin disease and offers new routes for finding treatments— Professor Muzlifah Haniffa
Human Cell Atlas
Part of the global Human Cell Atlas effort to map every cell type in the human body, the new comprehensive atlas of developing and adult skin is a valuable resource for scientists worldwide. It could also provide a template for regenerative medicine, helping researchers grow skin in the laboratory more effectively.Professor Muzlifah Haniffa, co-senior author from Newcastle University and Associate Faculty at the Wellcome Sanger Institute, said: “This Skin Cell Atlas reveals specific molecular signals sent by healthy developing skin to summon immune cells and form a protective layer. “We were amazed to see that eczema and psoriasis skin cells were sending the same molecular signals, which could over activate immune cells and cause the disease. This had never been seen before. “Discovering that developing cell pathways re-emerge is a huge leap in our understanding of inflammatory skin disease and offers new routes for finding treatments.” Our skin acts as a barrier, protecting us against invading bacteria or viruses, and is vital for health. Inflammatory skin diseases such as atopic eczema and psoriasis are chronic conditions, where the immune system becomes overactive, causing itchy or flaky skin that can be very painful and prone to infection.
These conditions can have significant impact on people’s lives, but the trigger is unknown and there is no cure, with treatments only helping to relieve the symptoms, not the cause.
To learn how skin forms and how this relates to adult health and disease, the researchers studied cells from developing skin, comparing these with biopsies from healthy adults, and eczema and psoriasis patients.
Using cutting-edge single cell technology and machine learning, the team analysed more than half a million individual skin cells, to see exactly which genes were switched on in each cell. This allowed them to find out what each individual cell does and how the cells talk to each other.
To their surprise, the researchers discovered that the diseased skin cells shared many of the same cellular mechanisms as developing cells.
Dr Gary Reynolds, a first author on the study from Newcastle University, said: “While our study focused on inflammatory skin disease, there is potential that other inflammatory diseases such as rheumatoid arthritis or inflammatory bowel disease could be triggered in the same way.
The study uncovered how healthy skin tissue develops and revealed the cells that are present in adult skin. This has great implications for regenerative medicine, especially for burns victims.
Dr Sarah Teichmann co-senior author from the Wellcome Sanger Institute and University of Cambridge, and co-chair of the Human Cell Atlas initiative, said: “Part of the international Human Cell Atlas initiative to create a ‘Google map’ of the human body, this skin cell atlas study reveals that studying development can not only help understand how tissues are formed in the first place, but also shed vital light on diseases.
“This map reveals a completely new way of thinking about inflammatory diseases and is an important reference that other scientists can use to investigate the causes of disease and inform potential new treatments.”
This study was supported by the Wellcome Human Cell Atlas Strategic Science Support, with additional funding from Wellcome, The Lister Institute for Preventive Medicine, NIHR Newcastle Biomedical Research Centre, the ERC, the EU and other sources.
Featured image: Professor Muzlifah Haniffa © NU
Reference: Gary Reynolds, Peter Vegh, James Fletcher, Elizabeth F. M. Poyner, Emily Stephenson, Issac Goh, Rachel A. Botting, Ni Huang, Bayanne Olabi, Anna Dubois, David Dixon, Kile Green, Daniel Maunder, Justin Engelbert, Mirjana Efremova, Krzysztof Polański, Laura Jardine, Claire Jones, Thomas Ness, Dave Horsfall, Jim McGrath, Christopher Carey, Dorin-Mirel Popescu, Simone Webb, Xiao-nong Wang, Ben Sayer, Jong-Eun Park, Victor A. Negri, Daria Belokhvostova, Magnus D. Lynch, David McDonald, Andrew Filby, Tzachi Hagai, Kerstin B. Meyer, Akhtar Husain, Jonathan Coxhead, Roser Vento-Tormo, Sam Behjati, Steven Lisgo, Alexandra-Chloé Villani, Jaume Bacardit, Philip H. Jones, Edel A. O’Toole, Graham S. Ogg, Neil Rajan, Nick J. Reynolds, Sarah A. Teichmann, Fiona M. Watt, Muzlifah Haniffa. Developmental cell programs are co-opted in inflammatory skin disease. Science, 2021; 371 (6527): eaba6500 DOI: DOI: 10.1126/science.aba6500
Provided by Newcastle University