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| Status |
Public on Mar 08, 2022 |
| Title |
Downregulation of WT1 transcription factor gene expression is required to promote myocardial fate [RNA-seq] |
| Organism |
Danio rerio |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
During cardiac development, cells from the precardiac mesoderm fuse to form the primordial heart tube, which then grows by addition of further progenitors to the venous and arterial poles. In the zebrafish, wilms tumor 1 transcription factor a (wt1a) and b (wt1b) are expressed in the pericardial mesoderm at the venous pole of the forming heart tube. The pericardial mesoderm forms a single layered mesothelial sheet that contributes to further the growth of the myocardium, and forms the proepicardium. Proepicardial cells are subsequently transferred to the myocardial surface and give rise to the epicardium, the outer layer covering the myocardium in the adult heart. wt1a/b expression is downregulated during the transition from pericardium to myocardium, but remains high in proepicardial cells. Here we show that sustained wt1 expression impaired cardiomyocyte maturation including sarcomere assembly, ultimately affecting heart morphology and cardiac function. ATAC-seq data analysis of cardiomyocytes overexpressing wt1 revealed that chromatin regions associated with myocardial differentiation genes remain closed upon wt1b overexpression in cardiomyocytes, suggesting that wt1 represses a myocardial differentiation program. Indeed, a subset of wt1a/b-expressing cardiomyocytes changed their cell adhesion properties, delaminated from the myocardial epithelium, and upregulated the expression of epicardial genes, as confirmed by in vivo imaging. Thus, we conclude that wt1 acts as a break for cardiomyocyte differentiation by repressing chromatin opening at specific genomic loci and that sustained ectopic expression of wt1 in cardiomyocytes can lead to their transformation into epicardial cells.
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| Overall design |
Dorsal pericardium, proepicardium and heart-tube were manually dissected, with tungsten needles, from 60 hpf epi:eGFP;myl7:mRFP zebrafish larvae. A minimum of 10 of each tissue/organ were collected and pooled for each sample. For pericardium, two samples were analysed. For the proepicardium 3 samples were analysed. For heart tube 3 samples were analysed.
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| Contributor(s) |
Marques I, Ernst A, Arora P, Vianin A, Hetke T, Sanz-Morejón A, Naumann U, Odriozola A, Langa X, Andrés-Delgado L, Haberthür D, Zuber B, Torroja C, Hlushchuk R, Osterwalder M, Simões F, Englert C, Mercader N |
| Citation(s) |
35312773 |
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| Submission date |
Jul 06, 2021 |
| Last update date |
Apr 20, 2022 |
| Contact name |
Nadia Mercader |
| E-mail(s) |
nmercader@cnic.es, nadia.mercader@unibe.ch
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| Organization name |
University of Bern
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| Street address |
Baltzerstrasse 2
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| City |
Bern |
| ZIP/Postal code |
3012 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL18413 |
Illumina HiSeq 2500 (Danio rerio) |
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| Samples (9)
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| This SubSeries is part of SuperSeries: |
| GSE179522 |
Downregulation of WT1 transcription factor gene expression is required to promote myocardial fate |
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| Relations |
| BioProject |
PRJNA744141 |
| SRA |
SRP327145 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE179520_normalized_counts.csv.gz |
1.6 Mb |
(ftp)(http) |
CSV |
| GSE179520_raw_counts.csv.gz |
424.4 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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