A prenatal skin atlas reveals immune regulation of human skin morphogenesis
Nusayhah Hudaa Gopee,
Elena Winheim,
Bayanne Olabi,
Chloe Admane,
April Rose Foster,
Ni Huang,
Rachel A. Botting,
Fereshteh Torabi,
Dinithi Sumanaweera,
Anh Phuong Le,
Jin Kim,
Luca Verger,
Emily Stephenson,
Diana Adão,
Clarisse Ganier,
Kelly Y. Gim,
Sara A. Serdy,
CiCi Deakin,
Issac Goh,
Lloyd Steele,
Karl Annusver,
Mohi-Uddin Miah,
Win Min Tun,
Pejvak Moghimi,
Kwasi Amoako Kwakwa,
Tong Li,
Daniela Basurto Lozada,
Ben Rumney,
Catherine L. Tudor,
Kenny Roberts,
Nana-Jane Chipampe,
Keval Sidhpura,
Justin Englebert,
Laura Jardine,
Gary Reynolds,
Antony Rose,
Vicky Rowe,
Sophie Pritchard,
Ilaria Mulas,
James Fletcher,
Dorin-Mirel Popescu,
Elizabeth Poyner,
Anna Dubois,
Alyson Guy,
Andrew Filby,
Steven Lisgo,
Roger A. Barker,
Ian A. Glass,
Jong-Eun Park,
Roser Vento-Tormo,
Marina Tsvetomilova Nikolova,
Peng He,
John E. G. Lawrence,
Josh Moore,
Stephane Ballereau,
Christine B. Hale,
Vijaya Shanmugiah,
David Horsfall,
Neil Rajan,
John A. McGrath,
Edel A. O’Toole,
Barbara Treutlein,
Omer Bayraktar,
Maria Kasper,
Fränze Progatzky,
Pavel Mazin,
Jiyoon Lee,
Laure Gambardella,
Karl R. Koehler (),
Sarah A. Teichmann () and
Muzlifah Haniffa ()
Additional contact information
Nusayhah Hudaa Gopee: Newcastle University
Elena Winheim: Wellcome Genome Campus, Hinxton
Bayanne Olabi: Newcastle University
Chloe Admane: Newcastle University
April Rose Foster: Wellcome Genome Campus, Hinxton
Ni Huang: Wellcome Genome Campus, Hinxton
Rachel A. Botting: Newcastle University
Fereshteh Torabi: Wellcome Genome Campus, Hinxton
Dinithi Sumanaweera: Wellcome Genome Campus, Hinxton
Anh Phuong Le: Boston Children’s Hospital
Jin Kim: Boston Children’s Hospital
Luca Verger: University of Oxford
Emily Stephenson: Newcastle University
Diana Adão: Wellcome Genome Campus, Hinxton
Clarisse Ganier: King’s College London Guy’s Hospital
Kelly Y. Gim: Boston Children’s Hospital
Sara A. Serdy: Boston Children’s Hospital
CiCi Deakin: Boston Children’s Hospital
Issac Goh: Newcastle University
Lloyd Steele: Wellcome Genome Campus, Hinxton
Karl Annusver: Karolinska Institutet
Mohi-Uddin Miah: Newcastle University
Win Min Tun: Newcastle University
Pejvak Moghimi: Wellcome Genome Campus, Hinxton
Kwasi Amoako Kwakwa: Wellcome Genome Campus, Hinxton
Tong Li: Wellcome Genome Campus, Hinxton
Daniela Basurto Lozada: Newcastle University
Ben Rumney: Wellcome Genome Campus, Hinxton
Catherine L. Tudor: Wellcome Genome Campus, Hinxton
Kenny Roberts: Wellcome Genome Campus, Hinxton
Nana-Jane Chipampe: Wellcome Genome Campus, Hinxton
Keval Sidhpura: Newcastle University
Justin Englebert: Newcastle University
Laura Jardine: Newcastle University
Gary Reynolds: Newcastle University
Antony Rose: Newcastle University
Vicky Rowe: Wellcome Genome Campus, Hinxton
Sophie Pritchard: Wellcome Genome Campus, Hinxton
Ilaria Mulas: Wellcome Genome Campus, Hinxton
James Fletcher: Newcastle University
Dorin-Mirel Popescu: Newcastle University
Elizabeth Poyner: Newcastle University
Anna Dubois: Newcastle Hospitals NHS Foundation Trust
Alyson Guy: Synnovis, Guy’s Hospital
Andrew Filby: Newcastle University
Steven Lisgo: Newcastle University
Roger A. Barker: University of Cambridge
Ian A. Glass: Department of Pediatrics, Genetic Medicine, University of Washington
Jong-Eun Park: Wellcome Genome Campus, Hinxton
Roser Vento-Tormo: Wellcome Genome Campus, Hinxton
Marina Tsvetomilova Nikolova: ETH Zurich
Peng He: Wellcome Genome Campus, Hinxton
John E. G. Lawrence: Wellcome Genome Campus, Hinxton
Josh Moore: Gesellschaft für Mikroskopie und Bildanalyse
Stephane Ballereau: Wellcome Genome Campus, Hinxton
Christine B. Hale: Wellcome Genome Campus, Hinxton
Vijaya Shanmugiah: Wellcome Genome Campus, Hinxton
David Horsfall: Newcastle University
Neil Rajan: Newcastle University
John A. McGrath: King’s College London Guy’s Campus
Edel A. O’Toole: Queen Mary University of London
Barbara Treutlein: ETH Zurich
Omer Bayraktar: Wellcome Genome Campus, Hinxton
Maria Kasper: Karolinska Institutet
Fränze Progatzky: University of Oxford
Pavel Mazin: Wellcome Genome Campus, Hinxton
Jiyoon Lee: Boston Children’s Hospital
Laure Gambardella: Wellcome Genome Campus, Hinxton
Karl R. Koehler: Boston Children’s Hospital
Sarah A. Teichmann: Wellcome Genome Campus, Hinxton
Muzlifah Haniffa: Newcastle University
Nature, 2024, vol. 635, issue 8039, 679-689
Abstract:
Abstract Human prenatal skin is populated by innate immune cells, including macrophages, but whether they act solely in immunity or have additional functions in morphogenesis is unclear. Here we assembled a comprehensive multi-omics reference atlas of prenatal human skin (7–17 post-conception weeks), combining single-cell and spatial transcriptomics data, to characterize the microanatomical tissue niches of the skin. This atlas revealed that crosstalk between non-immune and immune cells underpins the formation of hair follicles, is implicated in scarless wound healing and is crucial for skin angiogenesis. We systematically compared a hair-bearing skin organoid (SkO) model derived from human embryonic stem cells and induced pluripotent stem cells to prenatal and adult skin1. The SkO model closely recapitulated in vivo skin epidermal and dermal cell types during hair follicle development and expression of genes implicated in the pathogenesis of genetic hair and skin disorders. However, the SkO model lacked immune cells and had markedly reduced endothelial cell heterogeneity and quantity. Our in vivo prenatal skin cell atlas indicated that macrophages and macrophage-derived growth factors have a role in driving endothelial development. Indeed, vascular network remodelling was enhanced following transfer of autologous macrophages derived from induced pluripotent stem cells into SkO cultures. Innate immune cells are therefore key players in skin morphogenesis beyond their conventional role in immunity, a function they achieve through crosstalk with non-immune cells.
Date: 2024
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DOI: 10.1038/s41586-024-08002-x
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