Vitamin C facilitates direct cardiac reprogramming by inhibiting reactive oxygen species

The research focuses on the strategy of direct reprogramming of fibroblasts into cardiomyocytes using Gata4, Mef2c, and Tbx5 (GMT) transcription factors. Despite the promise of this approach, its limited efficiency has been a major obstacle. we found hat Vitamin C (VitC) significantly increased the cardiac reprogramming efficiency in GMT-overexpressing fibroblasts, both in 2D and 3D models, and in both human and mouse cells.

This enhancement was correlated with an initial increase in reactive oxygen species (ROS) generation, followed by a reduction upon VitC treatment, which coincided with increased reprogramming efficiency. To further confirm the robust cardiac inducing effect of VitC on direct cardiac reprogramming efficiency and explore the underlying mechanisms, we performed RNA sequencing to identify the differentially expressed genes between Doxy alone and Doxy plus VitC group.