Objective To investigate the effect of Islet-1 on the process of mesenchymal stem cells (MSCs) differentiation into cardiomyocyte-like cells and its mechanism.Problem statement In the past years, MSCs have been focused on in many experimental trails because they were easily available and with the capacity of differentiating into cardiomyocyte-like cells.Studies have shown that histone acetylation and deacetylation regulation played an important role in the process of MSCs transformation into cardiomyocyte-like cells.But the exact mechanism of histone acetylation and deacetylation regulation during MSCs differentiating into cardiomyocyte-like cells is not yet determined.It was reported that the histone acetylases (HATs) and deacetylases (HADCs) markedly lack the cardiac specific gene binding sites.Therefore, HATs and HADCs can not specifically bind on the cardiac specific genes and regulate their expression directly.Islet-l, a subtype of the LIM-HD subfamily, contains a DNA binding site and two LIM domains, had a capacity of combining with GCN5, which is one of HATs family involved in cardiomyocyte, hepatocyte, bone and neuron differentiation.Many studies has demonstrated that Islet-1 is crucial to cardiac development and cardiomyocyte differentiation.We hypothesis that Islet-1 is a key factor during the progress of MSCs specifically differentiating into cardiomyocyte-like cells and its effect is probably through the histone acetylation and deacetylation modifications.Methods Lentiviral vectors that express Islet-1 (Lenti-Islet-1) were constructed and used for C3H10T1/2 cells transduction.Islet-1, Gata4, Nkx2.5 and Mef2c gene expression in the transfected C3H10T1/2 cells were detected by q-PCR.cTnT expression was detected by western blotting and immunofluorescent cytochemistry.Non-cardiac specific proteins ALB, BALP and GFAP were detected by western blotting, AFP, BGP and Nestin gene expression were detected by q-PCR.Histone acetylation level was determined by ChIP, q-PCR and Western blotting.Results The Lenti-Islet-1 transfection efficiency in C3H 10T 1/2 cells was 88.82% and the transfection efficiency in cells transfected with lentiviral vectors alone without Islet-1 gene (Lenti-N) was 90.12%.Expression of Islet-1 in cells transfected with Lenti-Islet-1 was higher than that in C3H 10T 1/2 cells without viral transfection or the cells transfected with Lenti-N.Morphologically, the cells overexpressing Islet-1 tended toward fibroblast cells and arranged the same direction.Enhanced expressions of Gata4, Nkx2.5 and Mef2c were observed in the cells overexpressing Islet-1 two weeks after Lenti-Islet-1 transfection.The expression of cTnT in these cells was observed as well.However, no expressions of ALB, BALP and GFAP were detected in all of the experimental cells.Furthermore, the expression of BGP, AFP and Nestin was not statistically discrepant in these three experimental groups (P>0.05).AcH3 relative amount in the cells overexpressing Islet-1 was increased, which was associated with an enhanced expression of Gata4, Nkx2.5 and Mef2c in these cells.Conclusion Islet-1 could promote the cardiac specific differentiation of C3H10T1/2 cells, probably through histone acetylation regulation.