Rna-Seq Data Analysis Found Hdac, Suz12 and Ezh2 As the Most Important Epigenetic Regulating Factors For Generating Cardiac Progenitor Cells Through Direct Reprogramming Strategy

Background and aim: heart diseases are the most significant cause of morbidity and mortality worldwide, which accounts for approximately 33% of all deaths [2]. recently, a cellular alchemy-like method, known as direct cardiac reprogramming (dcr) has been developed for direct conversion of somatic cells such as fibroblast to cardiomyocytes required for cardiac cell-based therapy. to this end, several studies have reported tfs and mirnas for dcr, but the efficiency of all dcr studies is low. analysis of rna-seq data of cardiac progenitors cells (cpcs) produced through dcr seems to be very useful for finding new tfs and mirnas, which can be used along with previously reported factors to enhance the efficiency the dcr strategies, as well as the quality of produced cpcs.methods: the rna-seq data set gse77375 was obtained from the geo database that included fibroblasts and induced cpcs (icpcs; generated via dcr strategy). differential expressed genes (degs) were investigated using galaxy (https://usegalaxy.org/) [with p values <0.05 and │logfc│≥1.5]. gene ontology (http://geneontology.org/) and kegg (https://www.genome.jp/kegg/) were used to observe the biological processes and pathways associated with the genes upregulated in icpcs. to find the tfs controlling the expression of upregulated genes, chea was used . we also predicted the mirnas targeting the fibroblasts specific genes (downregulated genes) using enrichr. finally, we constructed the protein-protein interaction network (ppi) using string (https://string-db.org/) to find most important factors, especially epigenetic regulating factors in icpcs.results: we found that 247 and 2057 genes were upregulated and downregulated in icpcs, respectively. the upregulated genes extensively involved in post-translational modification and extracellular matrix disassembly and organization. kegg pathway analysis showed that p53 and pi3k-akt signaling are the most significant pathways associated with upregulated genes in icpcs. tfs analysis revealed that the top tfs associated with up degs were tnk1, csnk2a2 and mapk10 and in the other hand the top tfs for down degs were jak2, mapk1 and ret. we also found that mmu-mir-27b-3p and mmu-mir-183-5p are the most important mirnas targeting downregulated genes in icpcs. ppi network construction of icpcs upregulated genes revealed that epigenetic regulating factors such as ezh2, hdac and suz12 are in the core of ppi network.conclusion: activation of signaling pathway (pi3k-akt), epigenetic regulating mechanism (histone acetylation and methylation) along with overexpression of mirnas (mir-27b-3p) might increase the quantity and the quality of icpcs required for cardiac cell-based therapy.