Myocardial Notch signaling reprograms cardiomyocytes to a conduction-like phenotype.
Circulation
; 126(9): 1058-66, 2012 Aug 28.
Article
en En
| MEDLINE
| ID: mdl-22837163
ABSTRACT
BACKGROUND:
Notch signaling has previously been shown to play an essential role in regulating cell fate decisions and differentiation during cardiogenesis in many systems including Drosophila, Xenopus, and mammals. We hypothesized that Notch may also be involved in directing the progressive lineage restriction of cardiomyocytes into specialized conduction cells. METHODS ANDRESULTS:
In hearts where Notch signaling is activated within the myocardium from early development onward, Notch promotes a conduction-like phenotype based on ectopic expression of conduction system-specific genes and cell autonomous changes in electrophysiology. With the use of an in vitro assay to activate Notch in newborn cardiomyocytes, we observed global changes in the transcriptome, and in action potential characteristics, consistent with reprogramming to a conduction-like phenotype.CONCLUSIONS:
Notch can instruct the differentiation of chamber cardiac progenitors into specialized conduction-like cells. Plasticity remains in late-stage cardiomyocytes, which has potential implications for engineering of specialized cardiovascular tissues.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Nodo Atrioventricular
/
Regulación del Desarrollo de la Expresión Génica
/
Miocitos Cardíacos
/
Receptor Notch1
/
Miocardio
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Circulation
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos