Modulation of murine adult cardiac progenitors differentiation through specific interventions on epigenetics, paracrine signaling & metabolism
(2019)
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- Authors
- Supervisors
- Balligand, Jean-Luc
- Abstract
- Adult cardiac progenitor cells (CPC) are an attractive option for cardiac cell therapy but the results of clinical studies are mitigated so far. In this thesis, we studied three levers that promote the differentiation of CPCs into cardiac myocytes. We identified epigenetic mechanisms and signaling through paracrine nitric oxide (NO) that promote acquisition by CPC of phenotypic features characteristic of more mature cardiac myocytes. These two mechanisms function through inhibition of the canonical Wnt/β-catenin pathway. We demonstrated that proliferative CPC are essentially glycolytic and that their differentiation is accompanied by a shift from glycolytic to a more oxidative metabolism with increased mitochondria; however, activators of AMPK-activated protein kinase (AMPK) known to stimulate mitochondrial biogenesis are not sufficient to improve CPC differentiation.
- Affiliations
Citations
André, E. (2019). Modulation of murine adult cardiac progenitors differentiation through specific interventions on epigenetics, paracrine signaling & metabolism. https://hdl.handle.net/2078.5/124458