TWIST1 controls cellular senescence and energy metabolism in mesenchymal stem cells

Abstract

AbstractMesenchymal stem cells (MSC) are promising cells for regenerative medicine therapies, because they can differentiate towards multiple cell lineages. However, heterogeneity in differentiation capacity is one of the main drawbacks that limit their use clinically. Differences in the occurrence of cellular senescence and in the expression of the senescence associated secretory phenotype (SASP) in MSC populations contribute to their heterogeneity. Here, we show the involvement of TWIST1 expression in the regulation of MSC senescence, demonstrating that silencing of TWIST1 in MSCs increased the occurrence of senescence. These senescent MSCs had a SASP that was different from irradiation-induced senescent MSCs. In addition, metabolic evaluation performed by the Seahorse XF apparatus showed that both TWIST1 silencing-induced and irradiation-induced senescent MSCs had a higher oxygen consumption compared to control MSCs, while TWIST1 silencing-induced senescent MSCs had a low extracellular acidification rate compared to the irradiation-induced senescent MSCs. Overall, our data indicate how TWIST1 regulation influences senescence in human MSCs and that TWIST1 silencing-induced senescence is characterized by a specific expression of the SASP and the metabolic state.