A prenatal skin atlas reveals immune regulation of human skin morphogenesis

• 成果类型: Article
• 署名作者: Gopee, Nusayhah Hudaa; Winheim, Elena; Olabi, Bayanne; Admane, Chloe; Foster, April Rose; Huang, Ni; Botting, Rachel A.; Torabi, Fereshteh; Sumanaweera, Dinithi; Le, Anh Phuong; Kim, Jin; Verger, Luca; Stephenson, Emily; Adao, Diana; Ganier, Clarisse; Gim, Kelly Y.; Serdy, Sara A.; Deakin, Cici; Goh, Issac; Steele, Lloyd; Annusver, Karl; Miah, Mohi-Uddin; Tun, Win Min; Moghimi, Pejvak; Kwakwa, Kwasi Amoako; Li, Tong; Lozada, Daniela Basurto; Rumney, Ben; Tudor, Catherine L.; Roberts, Kenny; Chipampe, Nana-Jane; Sidhpura, Keval; Englebert, Justin; Jardine, Laura; Reynolds, Gary; Rose, Antony; Rowe, Vicky; Pritchard, Sophie; Mulas, Ilaria; Fletcher, James; Popescu, Dorin-Mirel; Poyner, Elizabeth; Dubois, Anna; Guy, Alyson; Filby, Andrew; Lisgo, Steven; Barker, Roger A.; Glass, Ian A.; Park, Jong-Eun; Vento-Tormo, Roser; Nikolova, Marina Tsvetomilova; He, Peng; Lawrence, John E. G.; Moore, Josh; Ballereau, Stephane; Hale, Christine B.; Shanmugiah, Vijaya; Horsfall, David; Rajan, Neil; McGrath, John A.; O'Toole, Edel A.; Treutlein, Barbara; Bayraktar, Omer; Kasper, Maria; Progatzky, Franze; Mazin, Pavel; Lee, Jiyoon; Gambardella, Laure; Koehler, Karl R.; Teichmann, Sarah A.; Haniffa, Muzlifah
• 署名单位: Newcastle University - UK; Newcastle Upon Tyne Hospitals NHS Foundation Trust; Newcastle University - UK; Newcastle Upon Tyne Hospitals NHS Foundation Trust; Newcastle University - UK; Wellcome Trust Sanger Institute; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; University of Oxford; Kennedy Institute for Rheumatology; Karolinska Institutet; University of Cambridge; University of Cambridge; University of Washington; University of Washington Seattle; Swiss Federal Institutes of Technology Domain; ETH Zurich; University of California System; University of California San Francisco; University of London; King's College London; University of London; Queen Mary University London
• 刊物名称: Nature
• ISSN/ISSBN: 0028-4111
• DOI: 10.1038/s41586-024-08002-x
• 发表日期: 2024-11-21
• 页码: 679-+
• 关键词: hair follicle; t-cells; migration; differentiation; macrophages; ichthyosis; ligands; biology; repair

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.