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Ageing is Associated with an Insufficient Early Inflammatory Response of Lung Endothelial Cells in SARS-CoV-2 Infection

GSE260604 Mus musculus (mouse) RNA-seq (gene expression) 16 samples Submitted 2024/05/22 Platform GPL17021
At a glance

RNA-seq (gene expression) · mouse · 16 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Mus musculus (mouse)
Samples
16 samples: 4 × Lung endothelial cells_aged_mock, vs 4 × Lung endothelial cells_aged_SARS-CoV-2 infected, vs 4 × Lung endothelial cells_Young_mock, vs 4 × Lung endothelial cells_Young_SARS-CoV-2 infected,Groups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
Aging is associated with an insufficient early inflammatory response of lung endothelial cells in SARS-CoV-2 infectionFrontiers in immunology · 2024
Summary (written by the submitters)
Advanced age is associated with an increased susceptibility to Coronavirus Disease (COVID)-19 and more severe outcomes, although the underlying mechanisms are understudied. The lung endothelium is located next to infected epithelial cells and bystander inflammation may contribute to thromboinflammation and COVID-19-associated coagulopathy.
Read the full summary ↓
Here, we investigated age-associated SARS-CoV-2 pathogenesis and endothelial inflammatory responses using humanized K18-hACE2 mice. Survival was reduced to 20% in aged mice (85-112 weeks) versus 50% in young mice (12-15 weeks) at 10 days post infection (dpi). Bulk RNA-sequencing of endothelial cells from mock and infected mice at 2dpi of both age groups (aged: 72-85 weeks; young: 15 weeks) showed substantially lower significant differentially regulated genes in infected aged mice than in young mice (712 versus 2294 genes). Viral recognition and anti-viral pathways such as RIG-I-like receptor signaling, NOD-like receptor signaling and interferon signaling were regulated in response to SARS-CoV-2. Young mice showed several fold higher interferon responses (Ifitm3, Ifit1, Isg15, Stat1) and interferon-induced chemokines (Cxcl10 and Cxcl11) than aged mice. Endothelial cells from infected young mice displayed elevated expression of chemokines (Cxcl9, Ccl2) and leukocyte adhesion markers (Icam1) underscoring that inflammation of lung endothelium during infection could facilitate leukocyte adhesion and thromboinflammation. TREM1 and acute phase response signaling were particularly prominent in endothelial cells from infected young mice. Immunohistochemistry was unable to detect viral protein in pulmonary endothelium. In conclusion, our data demonstrate that the early host response of the endothelium to SARS-CoV-2 infection declines with aging, which could be a potential contributor to disease severity.
Published in
Aging is associated with an insufficient early inflammatory response of lung endothelial cells in SARS-CoV-2 infection
Subramaniam S, Kenney D, Jayaraman A et al. · Frontiers in immunology 2024 · PMID 38911865 · doi:10.3389/fimmu.2024.1397990
This dataset
Open GSE260604 in finder → Find more mouse RNA-seq datasets →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE260604_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1082321 and SRA study SRP492640. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38911865) ↗
Study design
4 × Lung endothelial cells_aged_mock, vs 4 × Lung endothelial cells_aged_SARS-CoV-2 infected, vs 4 × Lung endothelial cells_Young_mock, vs 4 × Lung endothelial cells_Young_SARS-CoV-2 infected,

Supports a case/control comparison: 8 samples read as cases, 8 as controls.

How we read this: 4 replicated groups read from 16 sample titles; they account for 16 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
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