Developmental cell programs are co-opted in inflammatory skin disease

被引：360

作者：

Reynolds, Gary ^{[1
]}

Vegh, Peter ^{[1
]}

Fletcher, James ^{[1
]}

Poyner, Elizabeth F. M. ^{[1
,2
,3
]}

Stephenson, Emily ^{[1
]}

Goh, Issac ^{[1
]}

Botting, Rachel A. ^{[1
]}

Huang, Ni ^{[4
]}

Olabi, Bayanne ^{[1
,5
]}

Dubois, Anna ^{[1
,2
,3
]}

Dixon, David ^{[1
]}

Green, Kile ^{[1
]}

Maunder, Daniel ^{[1
]}

Engelbert, Justin ^{[1
]}

Efremova, Mirjana ^{[4
]}

Polanski, Krzysztof ^{[4
]}

Jardine, Laura ^{[1
]}

Jones, Claire ^{[1
]}

Ness, Thomas ^{[1
]}

Horsfall, Dave ^{[1
]}

McGrath, Jim ^{[1
]}

Carey, Christopher ^{[1
]}

Popescu, Dorin-Mirel ^{[1
]}

Webb, Simone ^{[1
]}

Wang, Xiao-Nong ^{[1
]}

Sayer, Ben ^{[1
]}

Park, Jong-Eun ^{[4
]}

Negri, Victor A. ^{[6
]}

Belokhvostova, Daria ^{[6
]}

Lynch, Magnus D. ^{[6
]}

McDonald, David ^{[1
]}

Filby, Andrew ^{[1
]}

Hagai, Tzachi ^{[7
]}

Meyer, Kerstin B. ^{[4
]}

Husain, Akhtar ^{[8
]}

Coxhead, Jonathan ^{[1
]}

Vento-Tormo, Roser ^{[4
]}

Behjati, Sam ^{[4
,9
]}

Lisgo, Steven ^{[1
]}

Villani, Alexandra-Chloe ^{[10
,11
]}

Bacardit, Jaume ^{[12
]}

Jones, Philip H. ^{[4
,13
]}

O'Toole, Edel A. ^{[14
]}

Ogg, Graham S. ^{[15
]}

Rajan, Neil ^{[1
,2
,3
]}

Reynolds, Nick J. ^{[2
,3
,16
]}

Teichmann, Sarah A. ^{[4
,17
]}

Watt, Fiona M. ^{[6
]}

Haniffa, Muzlifah ^{[1
,2
,3
,4
]}

机构：

[1] Newcastle Univ, Biosci Inst, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England

[2] Newcastle Hosp NHS Fdn Trust, Dept Dermatol, Newcastle Upon Tyne NE2 4LP, Tyne & Wear, England

[3] Newcastle Hosp NHS Fdn Trust, NIHR Newcastle Biomed Res Ctr, Newcastle Upon Tyne NE2 4LP, Tyne & Wear, England

[4] Wellcome Sanger Inst, Wellcome Genome Campus, Cambridge CB10 1SA, England

[5] NHS Lothian, Dept Dermatol, Lauriston Bldg, Edinburgh EH3 9EN, Midlothian, Scotland

[6] Kings Coll London, Ctr Stem Cells & Regenerat Med, Guys Hosp Campus, London SE1 9RT, England

[7] Tel Aviv Univ, George S Wise Fac Life Sci, Shmunis Sch Biomed & Canc Res, IL-69978 Tel Aviv, Israel

[8] Royal Victoria Infirm, Dept Pathol, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England

[9] Univ Cambridge, Dept Paediat, Cambridge CB2 0SP, England

[10] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA

[11] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02129 USA

[12] Newcastle Univ, Sch Comp, Newcastle Upon Tyne NE4 5TG, Tyne & Wear, England

[13] Univ Cambridge, MRC Canc Unit, Cambridge CB2 0XZ, England

[14] Queen Mary Univ London, Ctr Cell Biol & Cutaneous Res, Blizard Inst, London, England

[15] Univ Oxford, Oxford Biomed Res Ctr, MRC Weatherall Inst Mol Med, MRC Human Immunol Unit, Oxford, England

[16] Newcastle Univ, Translat & Clin Res Inst, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England

[17] Univ Cambridge, Dept Phys, Cavendish Lab, Theory Condensed Matter Grp, Cambridge CB3 0HE, England

来源：

SCIENCE | 2021年 / 371卷 / 6527期

基金：

英国生物技术与生命科学研究理事会; 英国医学研究理事会; 英国惠康基金; 英国工程与自然科学研究理事会;

关键词：

INNATE LYMPHOID-CELLS; DENDRITIC CELLS; LANGERHANS CELLS; GENE-EXPRESSION; TH17; CELLS; T-CELLS; MACROPHAGES; MOUSE; DIFFERENTIATION; PSORIASIS;

D O I：

10.1126/science.aba6500

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页码：364 / +

页数：57

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