Identification of novel cardiac transcription factors involved in direct reprogramming of mouse fibroblasts to cardiac progenitor cells

Heart disease is one reason of morbidity worldwide which accounts for approximately ۳۳% of all deaths. Cardiac cells after myocardial infarction (MI) lose their function and become Oscar tissues. There is a new strategy that called direct reprogramming or Transdifferentiation, that explains how a somatic cell can be converted to another type of cell, without transition from pluripotent state. Therefore, this study helps to explore the key genes and transcription factors using by bioinformatics approach. The gene expression dataset GSE۶۱۴۸۶ and GSE۷۷۳۷۵ were extracted from the Gene Expression Omnibus database, and the Galaxy software was utilized to identify the Differentially Expressed Genes (DEGs) for all both study. Functional and enrichment analyses of the DEGs were performed by the EnrichR. Up-regulated genes and down-regulated genes consider cardiac progenitor- and fibroblast-specific genes, respectively. By using this database, we reach a list of kinases, microRNAs and the upstream transcription factors. in each step, we used VENNY to utilized common up genes. Then, the protein-protein interaction (PPI) network of the up-regulated genes was constructed and visualized using STRING database and Cytoscape software, respectively. CytoHubba used to utilized rank the important nodes (genes) of the PPI modules. Moreover, the upstream regulatory network and the miRNA-target interactions of the up-regulated DEGs were analyzed by the X۲K web and the miRTarBase respectively. Top ۱۰ transcription factors, kinases, and miRNAs were also determined. To the best of our knowledge, the association of SUZ۱۲, GATA۴, TBX۵, TBK۱, has-miR-۵۵۵ with direct reprogramming was reported for the first time. We hope that our data can shed light on the dark side of Direct reprogramming and create a new perspective.

کلیدواژه ها:

Bioinformatics ، Direct Reprogramming ، Cardiac progenitor cells ، Transcription factors ، Protein kinase ، Metabolite