Sublethal Caspase Activation Promotes Generation of Cardiomyocytes from Embryonic Stem Cells

Bulatovic, Ivana; Ibarra, Cristian; Osterholm, Cecilia; Wang, Heng; Beltran-Rodriguez, Antonio; Varas-Godoy, Manuel; Mansson-Broberg, Agneta; Uhlen, Per; Simon, Andras; Grinnemo, Karl-Henrik

Abstract

Generation of new cardiomyocytes is critical for cardiac repair following myocardial injury, but which kind of stimuli is most important for cardiomyocyte regeneration is still unclear. Here we explore if apoptotic stimuli, manifested through caspase activation, influences cardiac progenitor up-regulation and cardiomyocyte differentiation. Using mouse embryonic stem cells as a cellular model, we show that sublethal activation of caspases increases the yield of cardiomyocytes while concurrently promoting the proliferation and differentiation of c-Kit(+)/alpha-actinin(low)cardiac progenitor cells. A broad-spectrum caspase inhibitor blocked these effects. In addition, the caspase inhibitor reversed the mRNA expression of genes expressed in cardiomyocytes and their precursors. Our study demonstrates that sublethal caspase-activation has an important role in cardiomyocyte differentiation and may have significant implications for promoting cardiac regeneration after myocardial injury involving exogenous or endogenous cell sources.

Más información

Título según WOS: ID WOS:000351276300036 Not found in local WOS DB
Título de la Revista: PLOS ONE
Volumen: 10
Número: 3
Editorial: PUBLIC LIBRARY SCIENCE
Fecha de publicación: 2015
DOI:

10.1371/journal.pone.0120176

Notas: ISI