Dataset Information
Cardiac explant-derived cells are regulated by Notch-modulated mesenchymal transition.
Ontology highlight
ABSTRACT: Background
Progenitor cell therapy is emerging as a novel treatment for heart failure. However the molecular mechanisms regulating the generation of cardiac progenitor cells is not fully understood. We hypothesized that cardiac progenitor cells are generated from cardiac explant via a process similar to epithelial to mesenchymal transition (EMT).Methods/findings
Explant-derived cells were generated from partially digested atrial tissue. After 21 days in culture, c-Kit+ cells were isolated from cell outgrowth. The majority of explant-originated c-Kit+ cells expressed the epicardial marker Wt1. Cardiac cell outgrowth exhibits a temporal up-regulation of EMT-markers. Notch stimulation augmented, while Notch inhibition suppressed, mesenchymal transition in both c-Kit+ and c-Kit- cells. In c-Kit+ cells, Notch stimulation reduced, while Notch inhibition up-regulated pluripotency marker expressions such as Nanog and Sox2. Notch induction was associated with degradation of ?-catenin in c-Kit- cells. In contrast, Notch inhibition resulted in ?-catenin accumulation, acquisition of epitheloid morphology, and up-regulation of Wnt target genes in c-Kit- cells.Conclusion
Our study suggests that Notch-mediated reversible EMT process is a mechanism that regulates explant-derived c-Kit+ and c-Kit- cells.
SUBMITTER: Zakharova L
PROVIDER: S-EPMC3360598 | biostudies-literature | 2012
REPOSITORIES: biostudies-literature
Publications
Cardiac explant-derived cells are regulated by Notch-modulated mesenchymal transition.
PloS one 20120525 5
<h4>Background</h4>Progenitor cell therapy is emerging as a novel treatment for heart failure. However the molecular mechanisms regulating the generation of cardiac progenitor cells is not fully understood. We hypothesized that cardiac progenitor cells are generated from cardiac explant via a process similar to epithelial to mesenchymal transition (EMT).<h4>Methods/findings</h4>Explant-derived cells were generated from partially digested atrial tissue. After 21 days in culture, c-Kit+ cells were ...[more]