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Chromatin accessibility landscapes of skin cells in systemic sclerosis nominate dendritic cells in disease pathogenesis

Author

Listed:
  • Qian Liu

    (University of Science and Technology of China)

  • Lisa C. Zaba

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Ansuman T. Satpathy

    (Stanford University School of Medicine)

  • Michelle Longmire

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Wen Zhang

    (University of Science and Technology of China)

  • Kun Li

    (University of Science and Technology of China)

  • Jeffrey Granja

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Chuang Guo

    (University of Science and Technology of China)

  • Jun Lin

    (University of Science and Technology of China)

  • Rui Li

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Karen Tolentino

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Gabriela Kania

    (University Hospital Zurich)

  • Oliver Distler

    (University Hospital Zurich)

  • David Fiorentino

    (Stanford University School of Medicine)

  • Lorinda Chung

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Kun Qu

    (University of Science and Technology of China
    University of Science and Technology of China
    University of Science and Technology of China)

  • Howard Y. Chang

    (Stanford University School of Medicine
    Stanford University School of Medicine)

Abstract

Systemic sclerosis (SSc) is a disease at the intersection of autoimmunity and fibrosis. However, the epigenetic regulation and the contributions of diverse cell types to SSc remain unclear. Here we survey, using ATAC-seq, the active DNA regulatory elements of eight types of primary cells in normal skin from healthy controls, as well as clinically affected and unaffected skin from SSc patients. We find that accessible DNA elements in skin-resident dendritic cells (DCs) exhibit the highest enrichment of SSc-associated single-nucleotide polymorphisms (SNPs) and predict the degrees of skin fibrosis in patients. DCs also have the greatest disease-associated changes in chromatin accessibility and the strongest alteration of cell–cell interactions in SSc lesions. Lastly, data from an independent cohort of patients with SSc confirm a significant increase of DCs in lesioned skin. Thus, the DCs epigenome links inherited susceptibility and clinically apparent fibrosis in SSc skin, and can be an important driver of SSc pathogenesis.

Suggested Citation

  • Qian Liu & Lisa C. Zaba & Ansuman T. Satpathy & Michelle Longmire & Wen Zhang & Kun Li & Jeffrey Granja & Chuang Guo & Jun Lin & Rui Li & Karen Tolentino & Gabriela Kania & Oliver Distler & David Fior, 2020. "Chromatin accessibility landscapes of skin cells in systemic sclerosis nominate dendritic cells in disease pathogenesis," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19702-z
    DOI: 10.1038/s41467-020-19702-z
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