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

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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.