Francoeur Nicholas, Sen Rwik
Active Motif, Incorporated, 1914 Palomar Oaks Way, Suite 150, Carlsbad, CA 92008, USA.
J Dev Biol. 2021 Sep 25;9(4):40. doi: 10.3390/jdb9040040.
Heart disease is the leading cause of death in the United States and worldwide. Understanding the molecular mechanisms of cardiac development and regeneration will improve diagnostic and therapeutic interventions against heart disease. In this direction, zebrafish is an excellent model because several processes of zebrafish heart development are largely conserved in humans, and zebrafish has several advantages as a model organism. Zebrafish transcriptomic profiles undergo alterations during different stages of cardiac development and regeneration which are revealed by RNA-sequencing. ChIP-sequencing has detected genome-wide occupancy of histone post-translational modifications that epigenetically regulate gene expression and identified a locus with enhancer-like characteristics. ATAC-sequencing has identified active enhancers in cardiac progenitor cells during early developmental stages which overlap with occupancy of histone modifications of active transcription as determined by ChIP-sequencing. CRISPR-mediated editing of the zebrafish genome shows how chromatin modifiers and DNA-binding proteins regulate heart development, in association with crucial signaling pathways. Hence, more studies in this direction are essential to improve human health because they answer fundamental questions on cardiac development and regeneration, their differences, and why zebrafish hearts regenerate upon injury, unlike humans. This review focuses on some of the latest studies using state-of-the-art technology enabled by the elegant yet simple zebrafish.
心脏病是美国乃至全球的主要死因。了解心脏发育和再生的分子机制将改善针对心脏病的诊断和治疗干预措施。在这方面，斑马鱼是一种优秀的模型，因为斑马鱼心脏发育的几个过程在很大程度上与人类保守，并且斑马鱼作为一种模式生物具有多个优势。斑马鱼转录组图谱在心脏发育和再生的不同阶段会发生变化，这通过RNA测序得以揭示。染色质免疫沉淀测序（ChIP-sequencing）检测到了全基因组范围内组蛋白翻译后修饰的占据情况，这些修饰在表观遗传上调节基因表达，并鉴定出一个具有增强子样特征的位点。转座酶可及染色质测序（ATAC-sequencing）在早期发育阶段鉴定出心脏祖细胞中的活性增强子，这些增强子与通过ChIP-sequencing确定的活性转录组蛋白修饰的占据情况重叠。CRISPR介导的斑马鱼基因组编辑显示了染色质修饰剂和DNA结合蛋白如何与关键信号通路相关联来调节心脏发育。因此，在这个方向上进行更多研究对于改善人类健康至关重要，因为它们回答了关于心脏发育和再生、它们的差异以及为什么斑马鱼心脏在受伤后能够再生而人类不能等基本问题。本综述重点关注一些使用优雅而简单的斑马鱼所实现的最先进技术的最新研究。
