Project: “Single Cardiomyocyte ALlelic imbalancE in hypertrophic cardiomyopathy (SCALE)”
| Acronym | SCALE (Reference Number: JTC-2019_020) |
| Duration | 01/05/2020 - 30/04/2023 |
| Project Topic | Hypertrophic cardiomyopathy (HCM) is mainly caused by heterozygous mutations in sarcomeric genes. Patients express both the wild-type and the mutated allele. The fraction of the mutated allele differs between neighboring cardiomyocytes (CM) in cardiac tissue. This ‘cell-to-cell allelic imbalance’ is contributing to the disease. To address this problem, the members of the SCALE consortium will use patient-derived induced pluripotent stem cell (iPSC) differentiated to cardiomyocytes (CM) as well as a large collection of myectomy samples from HCM patients. We will isolate and analyze single cells by fluorescenceactivated cell sorting (FACS) or laser microdissection (LMD). Allele specific RNA expression and chromatin modulation will be analyzed down to a single cell level to identify potential mechanisms underlying HCM development. Lastly, we will modulate the cell-to-cell allelic imbalance to minimize the functional mosaicism. To achieve this we will interfere with cultured CMs using compounds that might revert the allelic imbalance as possible treatment options. |
| Network | ERA-CVD |
| Call | ERA-CVD Joint Transnational Call 2019 |
Project partner
| Number | Name | Role | Country |
|---|---|---|---|
| 1 | University Medical Center Utrecht | Coordinator | Netherlands |
| 2 | Hannover Medical School | Partner | Germany |
| 3 | University Hospital Puerta de Hierro Majadahonda | Partner | Spain |
| 4 | The Hospital University Institute-Institute of Cardiometabolism and Nutrition | Partner | France |