A prenatal skin atlas reveals immune regulation of human skin morphogenesis

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2024年10月16日

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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,
Muzlifah Haniffa

摘要

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.