Using Gene Regulatory Network to find central transcription factors in conversion of mouse cardiac fibroblast into cardiomyocyte

Human heart contain cardiomyocyte, vascular cells and cardiac fibroblast which first one is the most important in heart function and occupy about 75% of myocardial normal tissue volume. Transcription factors (TFs) regulate direct reprogramming of cardiac fibroblast into cardiomyocyte. We use gene regulatory network to identify most important TFs during this conversion. Method: Data were obtained from GEO server using GSE22292 accession number. RMA algorithm in Affymetrix Powerful Tool(APT) and fold change algorithm were used to raw data normalization and detection of differentially expressed (DE) genesrespectively. DAVID was used for functional clustering of DE genes Chip enrichment analysis was used in order to find(TFs). Network constructed using Cytoscape software v2.8.3. Cytoscape`s CentiScaPe v3.0 was applied to predict degree tofind central genes. Result: To construct gene regulatory network and determined most important TFs we compare week0 versus (vs) 2 and week 2vs 4during direct conversion of mouse fibroblast into cardiomyocyte. Results show 1522 DE genes for first stage and 91 DE genes belong to second one. Expression of DE genes regulates by 25 TFs in the first stage and 2 TFs belonged to second one. Constructed Gene regulatory network contain 1280 node and 4244 edge. Gene regulatory network centrality analysis shows 10 TFs include, SUZ12, SPI1, MTF2, EP300, SETDB1 as most central regulators . Degree parameter reveals SUZ12 as the most important TF by 497 interactions. Conclusion:Using of these TFs and manipulating of their expression may be help to improve the efficiency of direct reprogramming.

کلیدواژه ها:

Cardiac fibroblast ، cardiomyocyte ، Direct reprogramming ، Gene regulatory network ، transcription factor