A prenatal skin atlas reveals immune regulation of human skin morphogenesis.

Autor:	Gopee NH; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.; Department of Dermatology and NIHR Newcastle Biomedical Research Centre, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK., Winheim E; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Olabi B; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.; Department of Dermatology and NIHR Newcastle Biomedical Research Centre, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK., Admane C; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Foster AR; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Huang N; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Botting RA; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK., Torabi F; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Sumanaweera D; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Le AP; Department of Otolaryngology, Boston Children's Hospital, Boston, MA, USA.; Department of Plastic and Oral Surgery, Boston Children's Hospital, Boston, MA, USA.; F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA, USA., Kim J; Department of Otolaryngology, Boston Children's Hospital, Boston, MA, USA.; Department of Plastic and Oral Surgery, Boston Children's Hospital, Boston, MA, USA.; F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA, USA., Verger L; Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK., Stephenson E; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Adão D; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Ganier C; Centre for Gene Therapy and Regenerative Medicine, King's College London Guy's Hospital, London, UK., Gim KY; Department of Otolaryngology, Boston Children's Hospital, Boston, MA, USA.; Department of Plastic and Oral Surgery, Boston Children's Hospital, Boston, MA, USA.; F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA, USA., Serdy SA; Department of Otolaryngology, Boston Children's Hospital, Boston, MA, USA.; Department of Plastic and Oral Surgery, Boston Children's Hospital, Boston, MA, USA.; F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA, USA., Deakin C; Department of Otolaryngology, Boston Children's Hospital, Boston, MA, USA.; Department of Plastic and Oral Surgery, Boston Children's Hospital, Boston, MA, USA.; F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA, USA., Goh I; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Steele L; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Annusver K; Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden., Miah MU; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK., Tun WM; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Moghimi P; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Kwakwa KA; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Li T; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Basurto Lozada D; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK., Rumney B; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Tudor CL; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Roberts K; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Chipampe NJ; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Sidhpura K; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK., Englebert J; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK., Jardine L; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK., Reynolds G; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK., Rose A; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Rowe V; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Pritchard S; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Mulas I; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Fletcher J; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK., Popescu DM; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK., Poyner E; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.; Department of Dermatology and NIHR Newcastle Biomedical Research Centre, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK., Dubois A; Department of Dermatology and NIHR Newcastle Biomedical Research Centre, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK., Guy A; Rare Skin Disease Laboratory, Synnovis, Guy's Hospital, London, UK., Filby A; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK., Lisgo S; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK., Barker RA; Department of Clinical Neuroscience and Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK., Glass IA; Department of Pediatrics, Genetic Medicine, University of Washington, Seattle, WA, USA., Park JE; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Vento-Tormo R; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Nikolova MT; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland., He P; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.; Department of Pathology, University of California San Francisco, San Francisco, CA, USA., Lawrence JEG; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Moore J; German BioImaging, Gesellschaft für Mikroskopie und Bildanalyse, Konstanz, Germany., Ballereau S; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Hale CB; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Shanmugiah V; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Horsfall D; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK., Rajan N; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.; Department of Dermatology and NIHR Newcastle Biomedical Research Centre, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK., McGrath JA; St Johns Institute of Dermatology, King's College London Guy's Campus, London, UK., O'Toole EA; Centre for Cell Biology and Cutaneous Research, Blizard Institute, Queen Mary University of London, London, UK., Treutlein B; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland., Bayraktar O; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Kasper M; Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden., Progatzky F; Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK., Mazin P; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Lee J; Department of Otolaryngology, Boston Children's Hospital, Boston, MA, USA.; Department of Plastic and Oral Surgery, Boston Children's Hospital, Boston, MA, USA.; F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA, USA., Gambardella L; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Koehler KR; Department of Otolaryngology, Boston Children's Hospital, Boston, MA, USA. Karl.Koehler@childrens.harvard.edu.; Department of Plastic and Oral Surgery, Boston Children's Hospital, Boston, MA, USA. Karl.Koehler@childrens.harvard.edu.; F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA, USA. Karl.Koehler@childrens.harvard.edu., Teichmann SA; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK. sat1003@cam.ac.uk., Haniffa M; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK. mh32@sanger.ac.uk.; Department of Dermatology and NIHR Newcastle Biomedical Research Centre, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. mh32@sanger.ac.uk.; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK. mh32@sanger.ac.uk.
Jazyk:	angličtina
Zdroj:	Nature [Nature] 2024 Nov; Vol. 635 (8039), pp. 679-689. Date of Electronic Publication: 2024 Oct 16.
DOI:	10.1038/s41586-024-08002-x
Abstrakt:	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).)
Databáze:	MEDLINE
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