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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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    as
    1. Omar Khan & Josephine R. Giles & Sierra McDonald & Sasikanth Manne & Shin Foong Ngiow & Kunal P. Patel & Michael T. Werner & Alexander C. Huang & Katherine A. Alexander & Jennifer E. Wu & John Attanas, 2019. "TOX transcriptionally and epigenetically programs CD8+ T cell exhaustion," Nature, Nature, vol. 571(7764), pages 211-218, July.
    2. Francesca Alfei & Kristiyan Kanev & Maike Hofmann & Ming Wu & Hazem E. Ghoneim & Patrick Roelli & Daniel T. Utzschneider & Madlaina von Hoesslin & Jolie G. Cullen & Yiping Fan & Vasyl Eisenberg & Dirk, 2019. "TOX reinforces the phenotype and longevity of exhausted T cells in chronic viral infection," Nature, Nature, vol. 571(7764), pages 265-269, July.
    3. Ilias Angelidis & Lukas M. Simon & Isis E. Fernandez & Maximilian Strunz & Christoph H. Mayr & Flavia R. Greiffo & George Tsitsiridis & Meshal Ansari & Elisabeth Graf & Tim-Matthias Strom & Monica Nag, 2019. "An atlas of the aging lung mapped by single cell transcriptomics and deep tissue proteomics," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    4. Kyle J. Travaglini & Ahmad N. Nabhan & Lolita Penland & Rahul Sinha & Astrid Gillich & Rene V. Sit & Stephen Chang & Stephanie D. Conley & Yasuo Mori & Jun Seita & Gerald J. Berry & Joseph B. Shrager , 2020. "A molecular cell atlas of the human lung from single-cell RNA sequencing," Nature, Nature, vol. 587(7835), pages 619-625, November.
    5. Andreas M. Reimold & Neal N. Iwakoshi & John Manis & Prashanth Vallabhajosyula & Eva Szomolanyi-Tsuda & Ellen M. Gravallese & Daniel Friend & Michael J. Grusby & Frederick Alt & Laurie H. Glimcher, 2001. "Plasma cell differentiation requires the transcription factor XBP-1," Nature, Nature, vol. 412(6844), pages 300-307, July.
    6. Matthew J. Yousefzadeh & Rafael R. Flores & Yi Zhu & Zoe C. Schmiechen & Robert W. Brooks & Christy E. Trussoni & Yuxiang Cui & Luise Angelini & Kyoo-A Lee & Sara J. McGowan & Adam L. Burrack & Dong W, 2021. "An aged immune system drives senescence and ageing of solid organs," Nature, Nature, vol. 594(7861), pages 100-105, June.
    7. Tatsuya Tsukui & Kai-Hui Sun & Joseph B. Wetter & John R. Wilson-Kanamori & Lisa A. Hazelwood & Neil C. Henderson & Taylor S. Adams & Jonas C. Schupp & Sergio D. Poli & Ivan O. Rosas & Naftali Kaminsk, 2020. "Collagen-producing lung cell atlas identifies multiple subsets with distinct localization and relevance to fibrosis," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    8. Andrew C. Scott & Friederike Dündar & Paul Zumbo & Smita S. Chandran & Christopher A. Klebanoff & Mojdeh Shakiba & Prerak Trivedi & Laura Menocal & Heather Appleby & Steven Camara & Dmitriy Zamarin & , 2019. "TOX is a critical regulator of tumour-specific T cell differentiation," Nature, Nature, vol. 571(7764), pages 270-274, July.
    9. David F. Boyd & E. Kaitlynn Allen & Adrienne G. Randolph & Xi-zhi J. Guo & Yunceng Weng & Catherine J. Sanders & Resha Bajracharya & Natalie K. Lee & Clifford S. Guy & Peter Vogel & Wenda Guan & Yimin, 2020. "Exuberant fibroblast activity compromises lung function via ADAMTS4," Nature, Nature, vol. 587(7834), pages 466-471, November.
    10. Daniel L. Barber & E. John Wherry & David Masopust & Baogong Zhu & James P. Allison & Arlene H. Sharpe & Gordon J. Freeman & Rafi Ahmed, 2006. "Restoring function in exhausted CD8 T cells during chronic viral infection," Nature, Nature, vol. 439(7077), pages 682-687, February.
    11. Suoqin Jin & Christian F. Guerrero-Juarez & Lihua Zhang & Ivan Chang & Raul Ramos & Chen-Hsiang Kuan & Peggy Myung & Maksim V. Plikus & Qing Nie, 2021. "Inference and analysis of cell-cell communication using CellChat," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
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