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| Status |
Public on Mar 10, 2023 |
| Title |
An interferon gamma response signature links myocardial aging and immunosenescence |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Aging entails profound immunological transformations that can negatively impact the myocardial biology and predispose to myocardial diseases. However, preclinical research in the immune-cardiology field is mostly conducted in young healthy animals, which potentially weakens its translational relevance. Herein, we sought to investigate how the aging T-cell compartment impacts myocardial cell biology in elderly. By investigating the paired-wised age-related shifts in the heart and its draining lymph nodes, our study provides evidence for an increased myocardial IFN-gamma signaling, which is associated with inflammatory and metabolic shifts typically seen in heart failure (HF).
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| Overall design |
We phenotyped the antigen-experienced CD44high T cells purified from heart-draining lymph nodes of 2, 6, 12, and 18-months old C57BL/6 mice using single-cell RNA / T-cell receptor (TCR) sequencing (sc-seq). Simultaneously, we profiled all non-cardiomyocyte cell subsets purified from 2- and 18-months old hearts and integrated our data with publicly available cardiomyocyte sc-seq datasets. With aging, the heart-draining lymph node and myocardial T cells underwent spontaneous clonal expansion and exhibited an up-regulated pro-inflammatory transcription signature, marked by an increased interferon-g (IFN-g) production. In parallel, all major myocardial cell populations showed an increased IFN-g responsive signature with aging. In the aged cardiomyocytes, a stronger IFN-g response signature was paralleled by dampening of expression levels of transcripts related to most metabolic pathways, especially oxidative phosphorylation. Likewise, induced pluripotent stem cells-derived cardiomyocytes (iPSC-CM) exposed to chronic low grade IFN-g treatment showed a similar inhibition of metabolic activity.
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| Contributor(s) |
Ashour D, Rebs S, Arampatzi P, Saliba A, Dudek J, Schulz R, Hofmann U, Frantz S, Cochain C, Streckfuß-Bömeke K, Ramos GC |
| Citation(s) |
37141306 |
| Submission date |
Nov 02, 2022 |
| Last update date |
Jun 09, 2023 |
| Contact name |
Antoine-Emmanuel Saliba |
| E-mail(s) |
emmanuel.saliba@helmholtz-hzi.de
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| Phone |
+49-931-31-81341
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| Organization name |
Helmholtz Institute for RNA-based Infection Research
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| Street address |
Josef-Schneider-Straße 2 / D15
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| City |
Würzburg |
| ZIP/Postal code |
97080 |
| Country |
Germany |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (5)
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| Relations |
| BioProject |
PRJNA896939 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE217098_Heart_Aging.Robj.gz |
130.4 Mb |
(ftp)(http) |
ROBJ |
| GSE217098_LN_T_cells_Aging.Robj.gz |
60.1 Mb |
(ftp)(http) |
ROBJ |
| GSE217098_LN_T_cells_Aging_Productive_TCRs.Robj.gz |
41.3 Mb |
(ftp)(http) |
ROBJ |
| GSE217098_RAW.tar |
244.0 Mb |
(http)(custom) |
TAR (of CSV, FASTA, MTX, TSV) |
| GSE217098_Seurat_objects_data_processing_README.txt |
3.2 Kb |
(ftp)(http) |
TXT |
| GSE217098_Supplemental_table_I.xlsx |
10.4 Kb |
(ftp)(http) |
XLSX |
| GSE217098_feature_A1_3.csv.gz |
263 b |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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