Developmental cell programs are co-opted in inflammatory skin disease

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

Abstract

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.

Datasets

1. Human healthy adult skin scRNA-seq data
Metadata
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Developmental cell programs are co-opted in inflammatory skin disease

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Source data

https://cellxgene.cziscience.com/collections/73f82ac8-15cc-4fcd-87f8-5683723fce7f

Alias names

E-MTAB-8142, PMID33479125, PMC7611557

Cite this study

Reynolds, G., Vegh, P., Fletcher, J., Poyner, E.F., Stephenson, E., Goh, I., Botting, R.A., Huang, N., Olabi, B., Dubois, A. and Dixon, D., 2021. Developmental cell programs are co-opted in inflammatory skin disease. Science, 371(6527), p.eaba6500. https://doi.org/10.1126/science.aba6500