Gene Expression Analysis in AHR (Aryl Hydrocarbon Receptor)- Active Fibroblast Cells to Measure Factors for Dedifferentiation of Fibroblast to Stem Cells

Background and Aim: Aryl hydrocarbon receptor (AHR) transcriptionfactor play key roles in cell differentiation, apoptosis, response to toxicsubstances, and cell growth. It effects on the transcription of many genesin the nucleus (more than 200 genes). For example, NFKB, RelB andp300 genes that play an important role in the development of organisms.The activation of this transcription factor has a role in cell fate in B cellsand promoting epithelial to mesenchymal cells and it also has roles inmany stem cells.Methods: Human fibroblasts were cultured in a specific culture medium.Three samples were treated with DMSO-soluble TCDD and three sampleswere treated with DMSO as controls. After 24 hours, the extraction ofRNA was carried out and gene expression analysis was performed usinga microarray device. Data obtained by GEO 2R software were comparedand the expression of genes was analyzed. Then, the results wereanalyzed in Reactome and Gorilla software, and molecular pathwaystowards the creation of stem cells were analyzed.Results: After analyzes carried out by Reactome and Gorilla software,we found that expression of hypoxia-inducible factor 2A (HIF2A)gene, pluripotency regulator gene under decreased oxygen conditions,increase. In another molecular network, after transcription, OCT4(octamer-binding transcription factor 4), a marker for undifferentiatedcells, attach to the LN28. Sox2 and Nanog transcribe (Nanog is afactor for maintaining the ES cell self-renewal). Then, in on one of thepathways, Oct4, Sox2, and Nanog link to the Sox2 promoter and causemore transcription of this gene. In another pathway, Oct4, Sox2, Nanog,ZscAN10, PRDM14, SMAD2, FOXP1-ES bind to the Oct4 promoter andcause more transcription of this gene. Oct4, Sox2, NANOG, KLF4, PBX1,and SMAD2 bind to the Nanog promoter, and enhance the expression ofthis gene. Nanog, Sox2, and Oct4 are markers for embryonic stem cells.Conclusion: Stem cells are biological cells that have the ability toconvert to different cells. One of the best ways to obtain stem cells isthe transform of somatic cells into stem cells. In this study, with thebioinformatic analysis of the fibroblast cells that their AHR transcriptionfactor was activated, it was found that the expression of Nanog, LN28M,and Sox2 factors increased, which have a great effect on pluripotency.

کلیدواژه ها:

Aryl hydrocarbon receptor ، Stem cell ، Epigenetic ، Development