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

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 and Weiguo Cui ()
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Moujtaba Y. Kasmani: Medical College of Wisconsin
Paytsar Topchyan: Medical College of Wisconsin
Ashley K. Brown: Medical College of Wisconsin
Ryan J. Brown: Medical College of Wisconsin
Xiaopeng Wu: Blood Research Institute, Versiti Wisconsin
Yao Chen: Medical College of Wisconsin
Achia Khatun: Medical College of Wisconsin
Donia Alson: Blood Research Institute, Versiti Wisconsin
Yue Wu: University of Virginia
Robert Burns: Blood Research Institute, Versiti Wisconsin
Chien-Wei Lin: Medical College of Wisconsin
Matthew R. Kudek: Medical College of Wisconsin
Jie Sun: University of Virginia
Weiguo Cui: Medical College of Wisconsin

Nature Communications, 2023, vol. 14, issue 1, 1-19

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-42021-y

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