Chemical Enhancement of In Vitro and In Vivo Direct Cardiac Reprogramming.

ABSTRACT:

Background

Reprogramming of cardiac fibroblasts into induced cardiomyocyte-like cells in situ represents a promising strategy for cardiac regeneration. A combination of 3 cardiac transcription factors, Gata4, Mef2c, and Tbx5 (GMT), can convert fibroblasts into induced cardiomyocyte-like cells, albeit with low efficiency in vitro.

Methods

We screened 5500 compounds in primary cardiac fibroblasts to identify the pathways that can be modulated to enhance cardiomyocyte reprogramming.

Results

We found that a combination of the transforming growth factor-β inhibitor SB431542 and the WNT inhibitor XAV939 increased reprogramming efficiency 8-fold when added to GMT-overexpressing cardiac fibroblasts. The small molecules also enhanced the speed and quality of cell conversion; w

SUBMITTER: Mohamed TM 

PROVIDER: S-EPMC5340593 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature