Project description:Different single mutations on the same sarcomeric gene often cause distinct cardiomyopathy phenotypes as dilated (DCM) or hypertrophic cardiomyopathy (HCM). The key factors involved in this disease divergence is unknown and could be key for disease intervention.We generated isogenic familial DCM and HCM disease-specific human embryonic stem cells (hESCs) carrying the cTnT-DK210 and -DE160 mutation, respectively. Whole transcriptomic RNA-sequencing was used to identify the key gene involved in the earliest disease divergence of cTnT-DK210 caused DCM and cTnT-DE160 caused HCM. Results provide insight into the new molecular mechanisms underlying familial dilated cardiomyopathy.
2021-10-01 | GSE154097 | GEO
Project description:Exome sequencing of dilated cardiomyopathy
Project description:Importantly, mutations in nuclear envelope-encoding genes are the second-highest cause of familial dilated cardiomyopathy. One such nuclear envelope protein that causes cardiomyopathy in humans and affects mouse heart development is Lem2. However, its role in mechanically active tissue such as heart remains poorly understood.
Project description:Dilated cardiomyopathy (DCM) is the leading cause of heart failure and transplantation worldwide. We used iPSCs to model this disease and compared gene expression change before and after gene therapy of cardiomyocytes derived from DCM-specific iPSCs. We used microarrays to detail the global gene expression of patient specific iPSCs, iPSC-derived cardiomyocytes and its response to gene therapy. Skin fibroblasts and iPSCs derived from a family exhibiting familial dilated cardiomyopathy and H7 human ESCs were subjected to RNA extraction and hybridization on Affymetrix microarrays.Global gene expression pattern were compared and analyzed. Cardiomyocytes derived from iPSCs generated from this DCM family were treated with or without adenoriral Serca2a and subjected to RNA extraction and hybridization on Affymetrix microarrays. Global gene expression pattern were compared and analyzed.
