Constructing gene regulatory network of cardiomyocytes derived from various Transdifferentiation approaches

Heart disease is one of the most important and most common causes of death among adults and even children in worldwide. In recent years, a novel approach called transdifferentiation, has been devised. In this approach, differentiated cells, such as fibroblasts, which, under normal conditions, are unable to differentiate into other cells, are directly transformed into other differentiated cells, such as heart cells. Investigating on the effect of gene expression in the transdifferentiation process, can be helpful in better understanding in this approach. In the present study, the gene expression profiles of GSE۴۹۱۹۲ and GSE۵۵۸۲۰ were derived from Gene Expression Omnibus (GEO) database, further analyzed by R script. Then, through Limma package, statistical parameters adj.P.vlaue<۰.۰۵ and |LogFC|≤-۱.۵ and |LogFC|≥۱.۵ were applied to determine Differentially Expressed Genes (DEGs). The GO and KEGG analyses were conducted through Enrichr. The protein-protein interaction (PPI) network of the DEGs was established through STRING website, visualized by Cytoscape and further analyzed by MCODE. The cytoHubba plug-in was used to identify hub genes. Our analysis showed that ۴۰۰ and ۸۹۸ genes were upregulated in GSE۴۹۱۹۲ and GSE۵۵۸۲۰, respectively. Moreover, ۲۴۶ and ۸۹۴ genes were downregulated in GSE۴۹۱۹۲ and GSE۵۵۸۲۰, respectively. The analysis showed that HAND۲ ،GATA۴ ،MEF۲C, TBX۵, ISL۱ ،JUN and CREB are the most important TFs in the PPI network of direct reprogrammed cardiomyocytes. It was found that TBX۵, MEF۲C and ISL۱ were that hub genes in directly reprogrammed cardiomyocytes through both studies. These factors have been used recently in Transdifferentiation studies and led to improve the efficiency. We also found that the actin binding is the most enriched pathways in direct reprogramed cardiomyocytes. The results of this study might help to achieve a better and more accurate understanding of the cardiac reprogramming process by these two methods, as well as application of identified factors might increase the efficiency of cardiomyocytes generation via differentiation and Transdifferentiation.

کلیدواژه ها:

Cardiac direct reprogramming ، Fibroblasts ، Transcription Factors ، Small Molecule ، Bioinformatic