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