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Developmental cell programs are co-opted in inflammatory skin disease.


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.

SUBMITTER: Reynolds G 

PROVIDER: S-EPMC7611557 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Developmental cell programs are co-opted in inflammatory skin disease.

Reynolds Gary G   Vegh Peter P   Fletcher James J   Poyner Elizabeth F M EFM   Stephenson Emily E   Goh Issac I   Botting Rachel A RA   Huang Ni N   Olabi Bayanne B   Dubois Anna A   Dixon David D   Green Kile K   Maunder Daniel D   Engelbert Justin J   Efremova Mirjana M   Polański Krzysztof K   Jardine Laura L   Jones Claire C   Ness Thomas T   Horsfall Dave D   McGrath Jim J   Carey Christopher C   Popescu Dorin-Mirel DM   Webb Simone S   Wang Xiao-Nong XN   Sayer Ben B   Park Jong-Eun JE   Negri Victor A VA   Belokhvostova Daria D   Lynch Magnus D MD   McDonald David D   Filby Andrew A   Hagai Tzachi T   Meyer Kerstin B KB   Husain Akhtar A   Coxhead Jonathan J   Vento-Tormo Roser R   Behjati Sam S   Lisgo Steven S   Villani Alexandra-Chloé AC   Bacardit Jaume J   Jones Philip H PH   O'Toole Edel A EA   Ogg Graham S GS   Rajan Neil N   Reynolds Nick J NJ   Teichmann Sarah A SA   Watt Fiona M FM   Haniffa Muzlifah M  

Science (New York, N.Y.) 20210101 6527


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  ...[more]

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