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Single-Cell and Spatial Transcriptomic Analysis of Human Skin Delineates Intercellular Communication and Pathogenic Cells

Thrane, Kim (author)
KTH,Genteknologi,Science for Life Laboratory, SciLifeLab
Winge, Mårten C.G. (author)
Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA
Wang, Hongyu (author)
Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Black Family Stem Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA; School of Computer Science and Engineering, Northwestern Polytechnical University, Xi'an, China
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Chen, Larry (author)
Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Black Family Stem Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
Guo, Margaret G. (author)
Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA; Biomedical Informatics Program, Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, California, USA
Andersson, Alma (author)
KTH,Genteknologi,Science for Life Laboratory, SciLifeLab
Abalo, Xesús M (author)
KTH,Genteknologi,Science for Life Laboratory, SciLifeLab
Yang, Xue (author)
Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA
Kim, Daniel S. (author)
Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA; Biomedical Informatics Program, Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, California, USA
Longo, Sophia K. (author)
Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA
Soong, Brian Y. (author)
Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Black Family Stem Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
Meyers, Jordan M. (author)
Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA
Reynolds, David L. (author)
Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA
McGeever, Aaron (author)
Chan Zuckerberg Biohub San Francisco, San Francisco, California, USA
Demircioglu, Deniz (author)
Bioinformatics for Next Generation Sequencing Core, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
Hasson, Dan (author)
Bioinformatics for Next Generation Sequencing Core, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
Mirzazadeh, Reza (author)
KTH,Science for Life Laboratory, SciLifeLab,Genteknologi
Rubin, Adam J. (author)
Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA
Bae, Gordon H. (author)
Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA
Karkanias, Jim (author)
Chan Zuckerberg Biohub San Francisco, San Francisco, California, USA
Rieger, Kerri (author)
Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA
Lundeberg, Joakim (author)
KTH,Science for Life Laboratory, SciLifeLab,Genteknologi
Ji, Andrew L. (author)
Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Black Family Stem Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
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 (creator_code:org_t)
Elsevier BV, 2023
2023
English.
In: Journal of Investigative Dermatology. - : Elsevier BV. - 0022-202X .- 1523-1747. ; 143:11, s. 13-2177
Related links:
https://urn.kb.se/re...
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https://doi.org/10.1...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Epidermal homeostasis is governed by a balance between keratinocyte proliferation and differentiation with contributions from cell–cell interactions, but conserved or divergent mechanisms governing this equilibrium across species and how an imbalance contributes to skin disease are largely undefined. To address these questions, human skin single-cell RNA sequencing and spatial transcriptomics data were integrated and compared with mouse skin data. Human skin cell–type annotation was improved using matched spatial transcriptomics data, highlighting the importance of spatial context in cell-type identity, and spatial transcriptomics refined cellular communication inference. In cross-species analyses, we identified a human spinous keratinocyte subpopulation that exhibited proliferative capacity and a heavy metal processing signature, which was absent in mouse and may account for species differences in epidermal thickness. This human subpopulation was expanded in psoriasis and zinc-deficiency dermatitis, attesting to disease relevance and suggesting a paradigm of subpopulation dysfunction as a hallmark of the disease. To assess additional potential subpopulation drivers of skin diseases, we performed cell-of-origin enrichment analysis within genodermatoses, nominating pathogenic cell subpopulations and their communication pathways, which highlighted multiple potential therapeutic targets. This integrated dataset is encompassed in a publicly available web resource to aid mechanistic and translational studies of normal and diseased skin.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Dermatologi och venereologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Dermatology and Venereal Diseases (hsv//eng)

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