Exploring the association between the immune response and heart regeneration in Astyanax mexicanus

心肌梗塞由于供给心脏的血管中的血流的突然减少或中断而发展，并导致由该血管供应的心肌中不同程度的细胞死亡（Go等人，2013年）。每5例猝死中就有1例是由于心肌梗死，5年生存率为50%（Gerbin & Murry，2015）。目前的治疗策略是有限的，它们包括姑息药物、心脏移植（<0.1%的心力衰竭患者）和辅助心脏功能的机械装置（Murray等人，2012年）。由于人类心脏在损伤后不能自我再生，MI仍然是最重要的死亡原因之一。受损心脏组织的损伤反应已在组织和遗传水平上表征，但MI后诱导再生仍然难以捉摸。（Potts等人，2021年）。与人类相反，一些鱼可以在损伤后修复它们的心肌（Koth等人，2020年）。了解这些鱼类模型中控制再生的信号和机制可能有助于创造新的治疗靶点来刺激人类心脏。这个博士项目将使用Astyanax mexicanus鱼作为模型来了解再生能力的潜在机制。生活在河流中的鱼可以在受损后修复心脏，而洞穴鱼则失去了这种能力（Stockdale等人，2018）。将洞穴鱼与水面鱼进行比较，可以确定心脏再生的关键机制。为了更好地了解再生与瘢痕形成过程中发生的情况，将在该模型中进行空间RNA测序，以区分驱动再生或永久性损伤的差异。在单细胞敏感性的局部基因表达的表示将解决再生和非再生心脏组织之间的细胞分化，形态发生和免疫应答之间的复杂相互作用的关键差异。这个博士项目将有助于了解鱼的独特之处，它们可以修复自己的心脏，并将有助于找到修复人类心脏衰竭的方法。

Myocardial infarction develops due to the sudden decrease or interruption of the blood flow in the blood vessels that feed the heart and results in various degrees of cell death in the heart muscle supplied by that vessel (Go et al., 2013). One of every 5 sudden deaths is due to a myocardial infarction with a 50% survival rate over 5 years (Gerbin & Murry, 2015). Current treatment strategies are limited and they include palliative drugs, heart transplantation (<0.1% of the heart failure patients), and mechanical devices to assist cardiac function (Murray et al., 2012). As human heart cannot regenerate itself upon injury, MI remains one of the most important causes of death. The injury response of the damaged heart tissue has been characterized at the tissue and genetic level, but inducing regeneration after MI remains elusive. (Potts et al., 2021). In contrast to humans, some fish can repair their heart muscle after damage (Koth et al., 2020). Understanding the signals and mechanisms that govern regeneration in these fish models could be useful to create new therapeutic targets to stimulate human heart. This DPhil project will use the Astyanax mexicanus fish as a model to understand the underlying mechanisms of regenerative ability. The fish living in the rivers can repair their hearts after damage, whereas the cavefish have lost this ability (Stockdale et al. 2018). Comparing the cavefish with the surface fish allows to identify key mechanisms underlying heart regeneration. To better understand what is happening during the regeneration versus scarring processes, spatial RNA sequencing will be performed in in this model to distinguish differences that drive regeneration or permanent damage. Representation of local gene expression at single cell sensitivity will address the key differences in complex interplay between cellular differentiation, morphogenesis and immune response between regenerative and non-regenerative heart tissues. This DPhil project will help to understand what is so unique about fish that they can repair their hearts and will help find ways to repair the failing human heart.