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


Journal

Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511

Informations de publication

Date de publication:
22 01 2021
Historique:
received: 21 12 2019
revised: 03 09 2020
accepted: 01 12 2020
entrez: 22 1 2021
pubmed: 23 1 2021
medline: 26 2 2021
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 33479125
pii: 371/6527/eaba6500
doi: 10.1126/science.aba6500
pmc: PMC7611557
mid: EMS132468
pii:
doi:

Substances chimiques

Dermatologic Agents 0
Methotrexate YL5FZ2Y5U1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Medical Research Council
ID : MC_UU_12022/3
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U137881017
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 221052
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00008/5
Pays : United Kingdom
Organisme : Medical Research Council
ID : G116/150
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R006237/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 088555
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12010/5
Pays : United Kingdom

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2021, American Association for the Advancement of Science.

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Auteurs

Gary Reynolds (G)

Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

Peter Vegh (P)

Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

James Fletcher (J)

Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

Elizabeth F M Poyner (EFM)

Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Department of Dermatology and NIHR Newcastle Biomedical Research Centre, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne NE2 4LP, UK.

Emily Stephenson (E)

Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

Issac Goh (I)

Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

Rachel A Botting (RA)

Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

Ni Huang (N)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.

Bayanne Olabi (B)

Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Department of Dermatology, NHS Lothian, Lauriston Building, Edinburgh EH3 9EN, UK.

Anna Dubois (A)

Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Department of Dermatology and NIHR Newcastle Biomedical Research Centre, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne NE2 4LP, UK.

David Dixon (D)

Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

Kile Green (K)

Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

Daniel Maunder (D)

Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

Justin Engelbert (J)

Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

Mirjana Efremova (M)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.

Krzysztof Polański (K)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.

Laura Jardine (L)

Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

Claire Jones (C)

Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

Thomas Ness (T)

Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

Dave Horsfall (D)

Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

Jim McGrath (J)

Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

Christopher Carey (C)

Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

Dorin-Mirel Popescu (DM)

Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

Simone Webb (S)

Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

Xiao-Nong Wang (XN)

Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

Ben Sayer (B)

Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

Jong-Eun Park (JE)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.

Victor A Negri (VA)

Centre for Stem Cells and Regenerative Medicine, King's College London, Guy's Hospital Campus, London SE1 9RT, UK.

Daria Belokhvostova (D)

Centre for Stem Cells and Regenerative Medicine, King's College London, Guy's Hospital Campus, London SE1 9RT, UK.

Magnus D Lynch (MD)

Centre for Stem Cells and Regenerative Medicine, King's College London, Guy's Hospital Campus, London SE1 9RT, UK.

David McDonald (D)

Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

Andrew Filby (A)

Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

Tzachi Hagai (T)

Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.

Kerstin B Meyer (KB)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.

Akhtar Husain (A)

Department of Pathology, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, UK.

Jonathan Coxhead (J)

Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

Roser Vento-Tormo (R)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.

Sam Behjati (S)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Department of Paediatrics, University of Cambridge, Cambridge CB2 0SP, UK.

Steven Lisgo (S)

Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

Alexandra-Chloé Villani (AC)

Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA 02129, USA.

Jaume Bacardit (J)

School of Computing, Newcastle University, Newcastle upon Tyne NE4 5TG, UK.

Philip H Jones (PH)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
MRC Cancer Unit, University of Cambridge, Cambridge CB2 0XZ, UK.

Edel A O'Toole (EA)

Centre for Cell Biology and Cutaneous Research, Blizard Institute, Queen Mary University of London, London, UK.

Graham S Ogg (GS)

MRC Human Immunology Unit, Oxford Biomedical Research Centre, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.

Neil Rajan (N)

Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Department of Dermatology and NIHR Newcastle Biomedical Research Centre, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne NE2 4LP, UK.

Nick J Reynolds (NJ)

Department of Dermatology and NIHR Newcastle Biomedical Research Centre, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne NE2 4LP, UK.
Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

Sarah A Teichmann (SA)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK. st9@sanger.ac.uk fiona.watt@kcl.ac.uk m.a.haniffa@newcastle.ac.uk.
Theory of Condensed Matter Group, Cavendish Laboratory/Department of Physics, University of Cambridge, Cambridge CB3 0HE, UK.

Fiona M Watt (FM)

Centre for Stem Cells and Regenerative Medicine, King's College London, Guy's Hospital Campus, London SE1 9RT, UK. st9@sanger.ac.uk fiona.watt@kcl.ac.uk m.a.haniffa@newcastle.ac.uk.

Muzlifah Haniffa (M)

Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK. st9@sanger.ac.uk fiona.watt@kcl.ac.uk m.a.haniffa@newcastle.ac.uk.
Department of Dermatology and NIHR Newcastle Biomedical Research Centre, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne NE2 4LP, UK.
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.

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