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Lookup NU author(s): Dr Hudaa Gopee, Dr Bayanne Olabi, Chloe Admane, Dr Rachel Botting, Emily Stephenson, Mohi Miah, Dr Win Tun, Daniela Basurto Lozada, Keval Sidhpura, Dr Laura JardineORCiD, Dr Gary Reynolds, Antony Rose, James Fletcher, Dr Dorin-Mirel Popescu, Dr Elizabeth Poyner, Professor Andrew FilbyORCiD, Dr Steven LisgoORCiD, Dave Horsfall, Professor Neil RajanORCiD, Professor Muzlifah Haniffa
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© The Author(s) 2024.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.
Author(s): 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, Adao D, Ganier C, Gim KY, Serdy SA, Deakin C, Goh I, Steele L, Annusver K, Miah M-U, Tun WM, Moghimi P, Kwakwa KA, Li T, Basurto Lozada D, Rumney B, Tudor CL, Roberts K, Chipampe N-J, Sidhpura K, Englebert J, Jardine L, Reynolds G, Rose A, Rowe V, Pritchard S, Mulas I, Fletcher J, Popescu D-M, Poyner E, Dubois A, Guy A, Filby A, Lisgo S, Barker RA, Glass IA, Park J-E, 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, Haniffa M
Publication type: Article
Publication status: Published
Journal: Nature
Year: 2024
Pages: epub ahead of print
Online publication date: 16/10/2024
Acceptance date: 28/08/2024
Date deposited: 04/11/2024
ISSN (print): 0028-0836
ISSN (electronic): 1476-4687
Publisher: Nature Research
URL: https://doi.org/10.1038/s41586-024-08002-x
DOI: 10.1038/s41586-024-08002-x
Data Access Statement: The datasets generated and/or analysed during the current study are available in the following repositories. Prenatal scRNA-seq skin data are available from ArrayExpress under accession numbers E-MTAB-11343, E-MTAB-7407 and E-MTAB-13071; accompanying prenatal skin TCR sequencing data are available under accession E-MTAB-13065. More at https://www.nature.com/articles/s41586-024-08002-x#data-availability and https://www.nature.com/articles/s41586-024-08002-x#code-availability
PubMed id: 39415002
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