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Series GSE217098 Query DataSets for GSE217098
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
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).
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.
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
Phone +49-931-31-81341
Organization name Helmholtz Institute for RNA-based Infection Research
Street address Josef-Schneider-Straße 2 / D15
City Würzburg
ZIP/Postal code 97080
Country Germany
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (5)
GSM6705095 Tcells_LN_GEX
GSM6705096 Tcells_LN_VDJ
GSM6705097 Tcells_LN_FB
BioProject PRJNA896939

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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
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Raw data are available in SRA
Processed data provided as supplementary file

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