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| 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
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| 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.
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| Overall design |
RNA-sequencing on cardiomyocytes from 12 ventricule samples from mice of sham, hypertrophic or failing hearts.
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| 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 |
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| Submission date |
Oct 02, 2019 |
| Last update date |
Apr 21, 2022 |
| Contact name |
Cornelis J. Boogerd |
| E-mail(s) |
k.boogerd@hubrecht.eu
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| Organization name |
Hubrecht Institute
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| Department |
Developmental Biology and Stem Cell Research
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| Street address |
Uppsalalaan 8
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| City |
Utrecht |
| ZIP/Postal code |
3584CT |
| Country |
Netherlands |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (1) |
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| Relations |
| BioProject |
PRJNA575365 |
| SRA |
SRP223948 |
| 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 |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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