In my DPhil project, which is jointly supervised by Prof Roger Patient (MRC Weatherall Institute of Molecular Medicine) and Prof Paul Riley (Department of Physiology, Anatomy and Genetics), I investigate cellular heterogeneity in the embryonic zebrafish epicardium.
Adult zebrafish possess an outstanding capacity to regenerate cardiac tissue following injury. Heart regeneration is thought to mostly recapitulate embryonic heart development and is dependent on the epicardium, a layer of cells enveloping the heart muscle. However, there is evidence that the epicardium is not a completely homogeneous tissue and distinct epicardial cell populations might fulfil specific functions during heart regeneration and development.
To analyse whether there are distinct cell populations in the embryonic zebrafish epicardium I generated transgenic reporter lines that allow for simultaneous expression analysis of the major epicardial markers 'transcription factor 21'(tcf21), 'T-box 18' (tbx18) and 'Wilms' tumor 1b' (wt1b). I indeed found these factors to be heterogeneous in their epicardial expression and, via single cell sequencing, identified three distinct sub-populations of epicardial cells in the embryonic zebrafish heart. I am currently studying the functions of these epicardial sub-populations via cell type specific CRISPR/Cas9 mediated marker gene knock-out. These findings will provide novel information as to the role epicardial cells play during heart development and will inform experiments on adult zebrafish heart regeneration.
Prior to starting my DPhil at the University of Oxford I completed the BSc in Biosciences and the MSc in Molecular Biomedicine at the University of Muenster in Germany, doing my MSc thesis work in the group of Prof Wiebke Herzog on zebrafish vascular development.
Distinct epicardial gene regulatory programmes drive development and regeneration of the zebrafish heart
Weinberger M. et al, (2021)