Faculty Collaboration Database

A spatial sequencing atlas of age-induced changes in the lung during influenza infection. Nat Commun 2023 Oct 18;14(1):6597

Date

10/19/2023

Pubmed ID

37852965

Pubmed Central ID

PMC10584893

DOI

10.1038/s41467-023-42021-y

Scopus ID

2-s2.0-85174461444 (requires institutional sign-in at Scopus site)   2 Citations

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.

Author List

Kasmani MY, Topchyan P, Brown AK, Brown RJ, Wu X, Chen Y, Khatun A, Alson D, Wu Y, Burns R, Lin CW, Kudek MR, Sun J, Cui W

Authors

Matthew Kudek MD Assistant Professor in the Pediatrics department at Medical College of Wisconsin
Chien-Wei Lin PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aged
Animals
Endothelial Cells
Epithelial Cells
Female
Humans
Influenza, Human
Lung
Mice
Orthomyxoviridae Infections