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Series GSE138299 Query DataSets for GSE138299
Status Public on Sep 15, 2020
Title Gene expression profiling of hypertrophic and failing cardiomyocytes identifies new players in heart failure
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Aim - Pathological cardiac remodeling is characterized by cardiomyocyte hypertrophy and fibroblast activation, which can ultimately lead to heart failure (HF). Genome-wide expression analysis on heart tissue has been instrumental for the identification of molecular mechanisms at play. However, these data were based on signals derived from all cardiac cell types. Here we aimed for a more detailed view on molecular changes driving cardiomyocyte hypertrophy and failure to aid in the development of therapies to reverse maladaptive remodeling.
Methods and results - Utilizing cardiomyocyte-specific reporter mice exposed to pressure overload by transverse aortic banding (TAB), we obtained gene expression profiles of hypertrophic (one-week TAB) and failing (eight-weeks TAB) cardiomyocytes. We identified subsets of genes differentially regulated and specific for either stage. Among these, we found upregulation of known marker genes for HF, such as Nppb and Myh7. Additionally, we identified a set of genes specifically upregulated in failing cardiomyocytes and that so far have not been studied in HF, including the platelet isoform of phosphofructokinase (PFKP). Human cardiomyocytes subjected to 7-day NE/AngII treatment recapitulated the upregulation of the failure-induced genes indicating conservation. RNA-seq on failing and healthy human hearts confirmed increased expression for several failure-induced genes and allowed for expressional correlation to NPPB/MYH7. Finally, suppression of Pfkp in PE-treated primary cardiomyocytes reduced stress-induced gene expression and hypertrophy, suggesting a role in cardiomyocyte failure.
Conclusion - Using cardiomyocyte-specific transcriptomic analysis we identified novel failure-induced genes relevant for human HF, and show that PFKP is a conserved failure-induced gene that can modulate cardiomyocyte stress response.
Overall design RNA-sequencing on cardiomyocytes from 12 ventricule samples from mice of sham, hypertrophic or failing hearts.
Contributor(s) Vigil-Garcia M, Demkes CJ, Eding JE, Versteeg D, de Ruiter H, Perini I, Gladka MM, Asselbergs FW, Vink A, Harakalova M, Bossu A, Boogerd CJ, van Rooij E
Citation(s) 32717063
Submission date Oct 02, 2019
Last update date Apr 21, 2022
Contact name Cornelis J. Boogerd
Organization name Hubrecht Institute
Department Developmental Biology and Stem Cell Research
Street address Uppsalalaan 8
City Utrecht
ZIP/Postal code 3584CT
Country Netherlands
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (1)
GSM4104719 CMs TAB
BioProject PRJNA575365
SRA SRP223948

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Supplementary file Size Download File type/resource
GSE138299_RAW.tar 840.0 Kb (http)(custom) TAR (of TSV)
GSE138299_readme.txt 3.1 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data provided as supplementary file

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