Wt1 Genes Can Induce a Cardiomyocyte to Epicardial-like Cell Fate Transition

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I. J. Marques, A. Ernst, P. Arora, A. Vianin, T. Hetke, A. Sanz-Morejón, U. Naumann, A. Odriozola ,X. Langa, L. Andrés-Delgado, B. Zuber, C. Torroja, M. Osterwalder, F. C. Simões, C. Englert & N. Mercader:

Wt1 transcription factor impairs cardiomyocyte specification and drives a phenotypic switch from myocardium to epicardium

Development (2022) 149 (6): dev200375.

https://doi.org/10.1242/dev.200375

Using the zebrafish as an in vivo model for development, this study shows that sustained Wt1 ortholog expression in cardiomyocytes impaired their maturation including sarcomere assembly, ultimately affecting cardiac morphology and function. Indeed, a subset of wt1a- or wt1b-expressing cardiomyocytes changed their cell adhesion properties, delaminated from the myocardial epithelium and assumed an epicardium-like phenotype. From this study, it was concluded that Wt1 plays a yet undescribed role for cardiomyocyte differentiation by repressing chromatin opening at specific genomic loci and that sustained ectopic expression of wt1a or wt1b in cardiomyocytes can lead to their transformation into epicardial cells.