Molecular Mechanisms Of Direct Reprogramming Of Mouse Fibroblasts To Cardiomyocyte-Like Cells By Transcriptome Data Analysis

Adult mammals cardiomyocytes limited regeneration capacity, the current therapies cannot completely repair the damage of heart tissue. Ieda et al. successfully direct reprogrammed fibroblasts into cardiomyocytes for the first time by using 3 transcription factors(Gata4, Mef2c and Tbx5) in 2010, the induced cells presented cardiomyocytes similar phenotypes, and the experiments in vivo got a higher conversion efficiency. Our study aims to reveal the molecular mechanism of the mice fibroblasts directly reprogramming to cardiomyocytes, which provide new ideas for induced cardiomyocytes regeneration.Methods:4 series microarray datasets related to direct cardiac reprogramming were downloaded from GEO database. After filtrated, we got 24 fibroblasts and 43 cardiomyocyte-like cells. The RankProd algorithm based on fold change method was employed to identified differentially expressed genes of direct cardiac reprogramming with P<0.05 and|lgFC|>1. The further analysis of differentially expressed genes were conducted by the on-line tools:DAVID, ToppGene and STRING.Results:With four series of statistical data analysis, we got 210 differentially expressed genes in the process of direct cardiac reprogramming, including 115 up-regulated and 95 down-regulated. Further bioinformatics analysis of variations genes biological significance in the process of direct reprogramming suggested that Fabp4 and striated muscle contraction signal pathway play essential roles in direct cardiac reprogramming.Summary, this research identified several differentially expressed genes and signaling pathways played key roles in direct cardiac reprogramming process based on microarray expression data statistical analysis. These findings provide valuable clues for the more particular knowledge of the molecular mechanism in the fibroblasts directly reprogramming to cardiomyocytes.