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Developmental cell programs are co-opted in inflammatory skin disease

Lookup NU author(s): Dr Gary Reynolds, Dr Peter Vegh, Dr James Fletcher, Dr Beth Poyner, Emily Stephenson, Issac Goh, Dr Rachel Botting, Dr Bayanne Olabi, Dr Anna Dubois, David Dixon, Dr Kile Green, Dan Maunder, Justin Engelbert, Dr Laura Jardine, Claire Jones, Dave Horsfall, Jim McGrath, Dr Christopher Carey, Dr Dorin-Mirel Popescu, Simone Webb, Dr Xiao Wang, Dr David McDonald, Dr Andrew Filby, Dr Akhtar Husain, Dr Jonathan Coxhead, Dr Roser Vento-Tormo, Dr Steven Lisgo, Dr Jaume Bacardit, Dr Neil Rajan, Professor Nick Reynolds, Professor Muzlifah Haniffa

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Abstract

© 2021 American Association for the Advancement of Science. All rights reserved.The skin confers biophysical and immunological protection through a complex cellular network established early in embryonic development. We profiled the transcriptomes of more than 500,000 single cells from developing human fetal skin, healthy adult skin, and adult skin with atopic dermatitis and psoriasis. We leveraged these datasets to compare cell states across development, homeostasis, and disease. Our analysis revealed an enrichment of innate immune cells in skin during the first trimester and clonal expansion of disease-associated lymphocytes in atopic dermatitis and psoriasis. We uncovered and validated in situ a reemergence of prenatal vascular endothelial cell and macrophage cellular programs in atopic dermatitis and psoriasis lesional skin. These data illustrate the dynamism of cutaneous immunity and provide opportunities for targeting pathological developmental programs in inflammatory skin diseases.


Publication metadata

Author(s): Reynolds G, Vegh P, Fletcher J, Poyner EFM, Stephenson E, Goh I, Botting RA, Huang N, Olabi B, Dubois A, Dixon D, Green K, Maunder D, Engelbert J, Efremova M, Polański K, Jardine L, Jones C, Ness T, Horsfall D, McGrath J, Carey C, Popescu D-M, Webb S, Wang X-N, Sayer B, Park J-E, Negri VA, Belokhvostova D, Lynch MD, McDonald D, Filby A, Hagai T, Meyer KB, Husain A, Coxhead J, Vento-Tormo R, Behjati S, Lisgo S, Villani A-C, Bacardit J, Jones PH, O'Toole EA, Ogg GS, Rajan N, Reynolds NJ, Teichmann SA, Watt FM, Haniffa M

Publication type: Article

Publication status: Published

Journal: Science

Year: 2021

Volume: 371

Issue: 6527

Print publication date: 22/01/2021

Acceptance date: 02/04/2018

ISSN (print): 0036-8075

ISSN (electronic): 1095-9203

Publisher: American Association for the Advancement of Science

URL: https://doi.org/10.1126/science.aba6500

DOI: 10.1126/science.aba6500


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