WT1 transcription factor impairs cardiomyocyte specification and drives a phenotypic switch from myocardium to epicardium.

Marques, Ines J; Ernst, Alexander; Arora, Prateek; Vianin, Andrej; Hetke, Tanja; Sanz-Morejon, Andrés; Naumann, Uta; Odriozola, Adolfo; Langa, Xavier; Andrés-Delgado, Laura; Zuber, Benoît; Torroja, Carlos; Osterwalder, Marco; Simões, Filipa; Englert, Christoph; Mercader, Nadia (2022). WT1 transcription factor impairs cardiomyocyte specification and drives a phenotypic switch from myocardium to epicardium. Development, 149(6) The Company of Biologists 10.1242/dev.200375

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During development, the heart growths through addition of progenitor cells to the poles of the primordial heart tube. In the zebrafish, wilms tumor 1 transcription factor a (wt1a) and b (wt1b) are expressed in the pericardium, at the venous pole of the heart. From this pericardial layer, the proepicardium emerges. Proepicardial cells are subsequently transferred to the myocardial surface and form the epicardium, covering the myocardium. We found that while wt1a/b expression is maintained in proepicardial cells, it is downregulated in those pericardial cells contributing to cardiomyocytes from the developing heart. Sustained wt1 expression in cardiomyocytes reduced chromatin accessibility of specific genomic loci. Strikingly, a subset of wt1a/b-expressing cardiomyocytes changed their cell adhesion properties, delaminated from the myocardium and upregulated epicardial gene expression. Thus, wt1 acts as a break for cardiomyocyte differentiation and ectopic wt1 expression in cardiomyocytes can lead to their transdifferentiation into epicardial like cells.

Item Type:

Journal Article (Original Article)

Division/Institute:

09 Interdisciplinary Units > Microscopy Imaging Center (MIC)
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Functional Anatomy
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Topographical and Clinical Anatomy

UniBE Contributor:

dos Santos Marques, Ines Joao, Ernst, Alexander Uwe Johann, Arora, Prateek, Hetke, Tanja, Sanz Morejon, Andrés, Odriozola Quesada, Adolfo, Zuber, Benoît, Osterwalder, Marco, Mercader Huber, Nadia Isabel

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1477-9129

Publisher:

The Company of Biologists

Language:

English

Submitter:

Pubmed Import

Date Deposited:

23 Mar 2022 08:19

Last Modified:

05 Dec 2022 16:16

Publisher DOI:

10.1242/dev.200375

PubMed ID:

35312773

Uncontrolled Keywords:

Cardiomyocyte Cell fate Epicardium Heart development Wt1 Zebrafish

BORIS DOI:

10.48350/167849

URI:

https://boris.unibe.ch/id/eprint/167849

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