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

Myocardial to epicardial-like fate transition in a developing zebrafish heart imaged with STELLARIS Digital LightSheet microscopy

Wt1b-positive myocardial cell adopting an epicardial cell morphology.  wt1b-positive_myocardial_cell_adopting_an_epicardial_cell_morphology.jpg

The vertebrate heart initially forms from cells of the precardiac mesoderm, which fuse to form the primordial heart tube. This tube grows by addition of further progenitors at both ends and starts beating in the meantime. The Wilms tumor 1 transcription factor (Wt1) is expressed in the pericardial mesoderm at the poles of the forming heart but becomes downregulated in the precursor cells entering the heart tube.

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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.

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.

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