Modelling and decoding the mechanisms of left ventricular non compaction cardiomyopathy (A04)

左心室致密化不全心肌病的机制建模和解码 (A04)

• 批准号: 508081932
• 金额: --
• 依托单位: Europäisches Laboratorium für Molekularbiologie (EMBL)
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/508081932?language=en
• 关键词: Modelling; decoding; mechanisms; left; ventricular

Human left ventricular non-compaction cardiomyopathy (LVNC-CM) is a common, yet understudied, heart disease. Many LVNC-CM mutations impact developmental genes, including lamin A, suggesting that these cardiomyopathies have a developmental origin. Here, state-of-the-art 3D left-ventricle organoids and genome engineering are combined to model lamin A mutations. The impact of patient mutations on the differentiation and function of the left ventricle will be characterized using single-cell genomics. The impact of stress on the contractile properties of mutant organoids will be assessed. A04 will thereby reveal the mechanisms by which lamin A mutations predispose and induce LVNC disease.

人类左室非压实性心肌病（LVNC-CM）是一种常见的心脏疾病，但尚未得到充分的研究。许多lnc - cm突变影响发育基因，包括纤层蛋白A，这表明这些心肌病具有发育起源。在这里，最先进的3D左心室类器官和基因组工程相结合，以模拟层粘连蛋白A突变。患者突变对左心室分化和功能的影响将使用单细胞基因组学进行表征。将评估应力对突变类器官收缩特性的影响。因此，A04将揭示层合蛋白A突变易感性和诱导LVNC疾病的机制。