Implications of the Wilms' Tumor Suppressor Wt1 in Cardiomyocyte Differentiation.
Wilms’ tumor suppressor 1
cardiomyocyte differentiation
mouse embryonic stem cells
myocardial infarction
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
21 Apr 2021
21 Apr 2021
Historique:
received:
02
04
2021
revised:
19
04
2021
accepted:
20
04
2021
entrez:
30
4
2021
pubmed:
1
5
2021
medline:
29
5
2021
Statut:
epublish
Résumé
The Wilms' tumor suppressor Wt1 is involved in multiple developmental processes and adult tissue homeostasis. The first phenotypes recognized in Wt1 knockout mice were developmental cardiac and kidney defects. Wt1 expression in the heart has been described in epicardial, endothelial, smooth muscle cells, and fibroblasts. Expression of Wt1 in cardiomyocytes has been suggested but remained a controversial issue, as well as the role of Wt1 in cardiomyocyte development and regeneration after injury. We determined cardiac Wt1 expression during embryonic development, in the adult, and after cardiac injury by quantitative RT-PCR and immunohistochemistry. As in vitro model, phenotypic cardiomyocyte differentiation, i.e., the appearance of rhythmically beating clones from mouse embryonic stem cells (mESCs) and associated changes in gene expression were analyzed. We detected Wt1 in cardiomyocytes from embryonic day (E10.5), the first time point investigated, until adult age. Cardiac Wt1 mRNA levels decreased during embryonic development. In the adult, Wt1 was reactivated in cardiomyocytes 48 h and 3 weeks following myocardial infarction. Wt1 mRNA levels were increased in differentiating mESCs. Overexpression of Wt1(-KTS) and Wt1(+KTS) isoforms in ES cells reduced the fraction of phenotypically cardiomyocyte differentiated clones, which was preceded by a temporary increase in c-kit expression in Wt1(-KTS) transfected ES cell clones and induction of some cardiomyocyte markers. Taken together, Wt1 shows a dynamic expression pattern during cardiomyocyte differentiation and overexpression in ES cells reduces their phenotypical cardiomyocyte differentiation.
Identifiants
pubmed: 33919406
pii: ijms22094346
doi: 10.3390/ijms22094346
pmc: PMC8122684
pii:
doi:
Substances chimiques
WT1 Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
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