1. A prenatal skin atlas reveals immune regulation of human skin morphogenesis.
- Author
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Gopee NH, Winheim E, Olabi B, Admane C, Foster AR, Huang N, Botting RA, Torabi F, Sumanaweera D, Le AP, Kim J, Verger L, Stephenson E, Adão D, Ganier C, Gim KY, Serdy SA, Deakin C, Goh I, Steele L, Annusver K, Miah MU, Tun WM, Moghimi P, Kwakwa KA, Li T, Basurto Lozada D, Rumney B, Tudor CL, Roberts K, Chipampe NJ, Sidhpura K, Englebert J, Jardine L, Reynolds G, Rose A, Rowe V, Pritchard S, Mulas I, Fletcher J, Popescu DM, Poyner E, Dubois A, Guy A, Filby A, Lisgo S, Barker RA, Glass IA, Park JE, Vento-Tormo R, Nikolova MT, He P, Lawrence JEG, Moore J, Ballereau S, Hale CB, Shanmugiah V, Horsfall D, Rajan N, McGrath JA, O'Toole EA, Treutlein B, Bayraktar O, Kasper M, Progatzky F, Mazin P, Lee J, Gambardella L, Koehler KR, Teichmann SA, and Haniffa M
- Subjects
- Humans, Endothelial Cells cytology, Endothelial Cells metabolism, Female, Neovascularization, Physiologic immunology, Transcriptome, Human Embryonic Stem Cells cytology, Human Embryonic Stem Cells metabolism, Wound Healing genetics, Fetus cytology, Fetus immunology, Skin immunology, Skin cytology, Morphogenesis, Macrophages immunology, Macrophages cytology, Macrophages metabolism, Hair Follicle cytology, Hair Follicle embryology, Hair Follicle metabolism, Organoids cytology, Organoids metabolism, Induced Pluripotent Stem Cells cytology, Induced Pluripotent Stem Cells metabolism, Immunity, Innate, Atlases as Topic, Single-Cell Analysis
- 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 skin
1 . 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., Competing Interests: Competing interests: J.L. and K.R.K., with the Indiana University Research and Technology Corporation, have a patent relating to the methodology and composition of SkOs (PCT/US2016/058174). K.R.K. is a consultant for StemCell Technologies. All other authors declare no competing interests., (© 2024. The Author(s).)- Published
- 2024
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