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首页> 外文期刊>PLoS Genetics >Hand factor ablation causes defective left ventricular chamber development and compromised adult cardiac function
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Hand factor ablation causes defective left ventricular chamber development and compromised adult cardiac function

机译：手工要点消融导致左心室发育缺陷缺陷，成年心功能受损

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Coordinated cardiomyocyte growth, differentiation, and morphogenesis are essential for heart formation. We demonstrate that the bHLH transcription factors Hand1 and Hand2 play critical regulatory roles for left ventricle (LV) cardiomyocyte proliferation and morphogenesis. Using an LV-specific Cre allele (Hand1LV-Cre), we ablate Hand1-lineage cardiomyocytes, revealing that DTA-mediated cardiomyocyte death results in a hypoplastic LV by E10.5. Once Hand1-linage cells are removed from the LV, and Hand1 expression is switched off, embryonic hearts recover by E16.5. In contrast, conditional LV loss-of-function of both Hand1 and Hand2 results in aberrant trabeculation and thickened compact zone myocardium resulting from enhanced proliferation and a breakdown of compact zone/trabecular/ventricular septal identity. Surviving Hand1;Hand2 mutants display diminished cardiac function that is rescued by concurrent ablation of Hand-null cardiomyocytes. Collectively, we conclude that, within a mixed cardiomyocyte population, removal of defective myocardium and replacement with healthy endogenous cardiomyocytes may provide an effective strategy for cardiac repair.
机译：协调心肌细胞生长，分化和形态发生对心脏形成至关重要。我们证明了BHLH转录因子Hand1和Hand2对左心室（LV）心肌细胞增殖和形态发生起到严重的调节作用。使用LV特异性CRE等位基因（Hand1LV-CRE），我们烧蚀Hand1谱系心肌细胞，揭示DTA介导的心肌细胞死亡通过E10.5产生了Hypoplastic LV。一旦从LV移除了手1线细胞，并且关闭了Hand1表达，胚胎心脏通过E16.5恢复。相比之下，Hand1和Hand2的条件LV函数损失导致异常的三相结构和增厚的紧凑型心肌，这是由于增强的增殖和紧凑型/颌骨/心室隔膜身份的崩溃。存活Hand1; Hand2突变体显示了通过并发消融手中的心肌细胞来拯救的心脏功能减少。总的来说，我们得出结论，在混合的心肌细胞群中，除去缺陷的心肌和用健康内源性心肌细胞的替代物可以提供有效的心脏修复策略。

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