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

doi:10.1126/science.aba6500

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 HorsfallJim 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^*

^*Corresponding author for this work

The Shmunis School of Biomedicine and Cancer Research

Research output: Contribution to journal › Article › peer-review

256 Scopus citations

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.

Original language	English
Article number	eaba6500
Journal	Science
Volume	371
Issue number	6527
DOIs	https://doi.org/10.1126/science.aba6500
State	Published - 22 Jan 2021

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Reynolds, G., Vegh, P., Fletcher, J., Poyner, E. F. M., Stephenson, E., Goh, I., Botting, R. A., Huang, N., Olabi, B., Dubois, A., Dixon, D., Green, K., Maunder, D., Engelbert, J., Efremova, M., Polański, K., Jardine, L., Jones, C., Ness, T., ... Haniffa, M. (2021). Developmental cell programs are co-opted in inflammatory skin disease. Science, 371(6527), Article eaba6500. https://doi.org/10.1126/science.aba6500

@article{5e3cb36b16124379a1fc3990da472809,

title = "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.",

author = "Gary Reynolds and Peter Vegh and James Fletcher and Poyner, {Elizabeth F.M.} and Emily Stephenson and Issac Goh and Botting, {Rachel A.} and Ni Huang and Bayanne Olabi and Anna Dubois and David Dixon and Kile Green and Daniel Maunder and Justin Engelbert and Mirjana Efremova and Krzysztof Pola{\'n}ski and Laura Jardine and Claire Jones and Thomas Ness and Dave Horsfall and Jim McGrath and Christopher Carey and Popescu, {Dorin Mirel} and Simone Webb and Wang, {Xiao Nong} and Ben Sayer and Park, {Jong Eun} and Negri, {Victor A.} and Daria Belokhvostova and Lynch, {Magnus D.} and David McDonald and Andrew Filby and Tzachi Hagai and Meyer, {Kerstin B.} and Akhtar Husain and Jonathan Coxhead and Roser Vento-Tormo and Sam Behjati and Steven Lisgo and Villani, {Alexandra Chlo{\'e}} and Jaume Bacardit and Jones, {Philip H.} and O'Toole, {Edel A.} and Ogg, {Graham S.} and Neil Rajan and Reynolds, {Nick J.} and Teichmann, {Sarah A.} and Watt, {Fiona M.} and Muzlifah Haniffa",

year = "2021",

month = jan,

day = "22",

doi = "10.1126/science.aba6500",

language = "אנגלית",

volume = "371",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

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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, DM, Webb, S, Wang, XN, Sayer, B, Park, JE, 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, AC, Bacardit, J, Jones, PH, O'Toole, EA, Ogg, GS, Rajan, N, Reynolds, NJ, Teichmann, SA, Watt, FM & Haniffa, M 2021, 'Developmental cell programs are co-opted in inflammatory skin disease', Science, vol. 371, no. 6527, eaba6500. https://doi.org/10.1126/science.aba6500

TY - JOUR

T1 - Developmental cell programs are co-opted in inflammatory skin disease

AU - Reynolds, Gary

AU - Vegh, Peter

AU - Fletcher, James

AU - Poyner, Elizabeth F.M.

AU - Stephenson, Emily

AU - Goh, Issac

AU - Botting, Rachel A.

AU - Huang, Ni

AU - Olabi, Bayanne

AU - Dubois, Anna

AU - Dixon, David

AU - Green, Kile

AU - Maunder, Daniel

AU - Engelbert, Justin

AU - Efremova, Mirjana

AU - Polański, Krzysztof

AU - Jardine, Laura

AU - Jones, Claire

AU - Ness, Thomas

AU - Horsfall, Dave

AU - McGrath, Jim

AU - Carey, Christopher

AU - Popescu, Dorin Mirel

AU - Webb, Simone

AU - Wang, Xiao Nong

AU - Sayer, Ben

AU - Park, Jong Eun

AU - Negri, Victor A.

AU - Belokhvostova, Daria

AU - Lynch, Magnus D.

AU - McDonald, David

AU - Filby, Andrew

AU - Hagai, Tzachi

AU - Meyer, Kerstin B.

AU - Husain, Akhtar

AU - Coxhead, Jonathan

AU - Vento-Tormo, Roser

AU - Behjati, Sam

AU - Lisgo, Steven

AU - Villani, Alexandra Chloé

AU - Bacardit, Jaume

AU - Jones, Philip H.

AU - O'Toole, Edel A.

AU - Ogg, Graham S.

AU - Rajan, Neil

AU - Reynolds, Nick J.

AU - Teichmann, Sarah A.

AU - Watt, Fiona M.

AU - Haniffa, Muzlifah

PY - 2021/1/22

Y1 - 2021/1/22

N2 - 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.

AB - 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.

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DO - 10.1126/science.aba6500

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AN - SCOPUS:85099926955

SN - 0036-8075

VL - 371

JO - Science

JF - Science

IS - 6527

M1 - eaba6500

ER -

Developmental cell programs are co-opted in inflammatory skin disease

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