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  • Thrane, KimKTH,Genteknologi,Science for Life Laboratory, SciLifeLab (author)

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

  • Article/chapterEnglish2023

Publisher, publication year, extent ...

  • Elsevier BV,2023
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:kth-338543
  • https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-338543URI
  • https://doi.org/10.1016/j.jid.2023.02.040DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • QC 20231114
  • 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 and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Winge, Mårten C.G.Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA (author)
  • Wang, HongyuDepartment 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 (author)
  • Chen, LarryDepartment 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 (author)
  • Guo, Margaret G.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 (author)
  • Andersson, AlmaKTH,Genteknologi,Science for Life Laboratory, SciLifeLab(Swepub:kth)u15avt37 (author)
  • Abalo, Xesús MKTH,Genteknologi,Science for Life Laboratory, SciLifeLab(Swepub:kth)u1k6r84m (author)
  • Yang, XueProgram in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA (author)
  • Kim, Daniel S.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 (author)
  • Longo, Sophia K.Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA (author)
  • Soong, Brian Y.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 (author)
  • Meyers, Jordan M.Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA (author)
  • Reynolds, David L.Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA (author)
  • McGeever, AaronChan Zuckerberg Biohub San Francisco, San Francisco, California, USA (author)
  • Demircioglu, DenizBioinformatics for Next Generation Sequencing Core, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA (author)
  • Hasson, DanBioinformatics 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 (author)
  • Mirzazadeh, RezaKTH,Science for Life Laboratory, SciLifeLab,Genteknologi(Swepub:kth)u1z0z7ka (author)
  • Rubin, Adam J.Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA (author)
  • Bae, Gordon H.Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA (author)
  • Karkanias, JimChan Zuckerberg Biohub San Francisco, San Francisco, California, USA (author)
  • Rieger, KerriProgram in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA (author)
  • Lundeberg, JoakimKTH,Science for Life Laboratory, SciLifeLab,Genteknologi(Swepub:kth)u1qkn9kw (author)
  • Ji, Andrew L.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 (author)
  • KTHGenteknologi (creator_code:org_t)

Related titles

  • In:Journal of Investigative Dermatology: Elsevier BV143:11, s. 13-21770022-202X1523-1747

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