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A spatial sequencing atlas of age-induced changes in the lung during influenza infection

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  • Moujtaba Y. Kasmani

    (Medical College of Wisconsin
    Blood Research Institute, Versiti Wisconsin)

  • Paytsar Topchyan

    (Medical College of Wisconsin
    Blood Research Institute, Versiti Wisconsin)

  • Ashley K. Brown

    (Medical College of Wisconsin
    Blood Research Institute, Versiti Wisconsin)

  • Ryan J. Brown

    (Medical College of Wisconsin
    Blood Research Institute, Versiti Wisconsin)

  • Xiaopeng Wu

    (Blood Research Institute, Versiti Wisconsin)

  • Yao Chen

    (Medical College of Wisconsin
    Blood Research Institute, Versiti Wisconsin)

  • Achia Khatun

    (Medical College of Wisconsin
    Blood Research Institute, Versiti Wisconsin)

  • Donia Alson

    (Blood Research Institute, Versiti Wisconsin
    Medical College of Wisconsin)

  • Yue Wu

    (University of Virginia
    University of Virginia)

  • Robert Burns

    (Blood Research Institute, Versiti Wisconsin)

  • Chien-Wei Lin

    (Medical College of Wisconsin)

  • Matthew R. Kudek

    (Medical College of Wisconsin
    Blood Research Institute, Versiti Wisconsin
    Medical College of Wisconsin)

  • Jie Sun

    (University of Virginia
    University of Virginia)

  • Weiguo Cui

    (Medical College of Wisconsin
    Blood Research Institute, Versiti Wisconsin
    Northwestern University)

Abstract

Influenza virus infection causes increased morbidity and mortality in the elderly. Aging impairs the immune response to influenza, both intrinsically and because of altered interactions with endothelial and pulmonary epithelial cells. To characterize these changes, we performed single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and bulk RNA sequencing (bulk RNA-seq) on lung tissue from young and aged female mice at days 0, 3, and 9 post-influenza infection. Our analyses identified dozens of key genes differentially expressed in kinetic, age-dependent, and cell type-specific manners. Aged immune cells exhibited altered inflammatory, memory, and chemotactic profiles. Aged endothelial cells demonstrated characteristics of reduced vascular wound healing and a prothrombotic state. Spatial transcriptomics identified novel profibrotic and antifibrotic markers expressed by epithelial and non-epithelial cells, highlighting the complex networks that promote fibrosis in aged lungs. Bulk RNA-seq generated a timeline of global transcriptional activity, showing increased expression of genes involved in inflammation and coagulation in aged lungs. Our work provides an atlas of high-throughput sequencing methodologies that can be used to investigate age-related changes in the response to influenza virus, identify novel cell-cell interactions for further study, and ultimately uncover potential therapeutic targets to improve health outcomes in the elderly following influenza infection.

Suggested Citation

  • Moujtaba Y. Kasmani & Paytsar Topchyan & Ashley K. Brown & Ryan J. Brown & Xiaopeng Wu & Yao Chen & Achia Khatun & Donia Alson & Yue Wu & Robert Burns & Chien-Wei Lin & Matthew R. Kudek & Jie Sun & We, 2023. "A spatial sequencing atlas of age-induced changes in the lung during influenza infection," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42021-y
    DOI: 10.1038/s41467-023-42021-y
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