A prenatal skin atlas reveals immune regulation of human skin morphogenesis

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), combini...

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Published in:	Nature (London) Vol. 635; no. 8039; pp. 679 - 689
Main Authors:	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, Adão, 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, Basurto Lozada, Daniela, 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, Fränze, Mazin, Pavel, Lee, Jiyoon, Gambardella, Laure, Koehler, Karl R., Teichmann, Sarah A., Haniffa, Muzlifah
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 21-11-2024
Subjects:	13/1 13/100 13/106 13/31 14/63 38/32 45/91 631/114 631/136/16 631/136/1660 631/250/2504/342/1952 631/532/2064/2158 82/80 Humanities and Social Sciences multidisciplinary Science Science (multidisciplinary)
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Summary:	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. A comprehensive multi-omics reference atlas of prenatal human skin shows that innate immune cells crosstalk with non-immune cells to perform pivotal roles in skin morphogenesis, including the formation of hair follicles.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0028-0836 1476-4687 1476-4687
DOI:	10.1038/s41586-024-08002-x