Investigation Of Differentially Expressed Genes Involved In Induced-Resembled Neuronal Cells From Melanoma By Different Genes Based On RNA-Seq

Purpose: MC-irNCs(melanoma cell-induced-resembled neuronal cells) were induced by different protocols. For the advantage of RNA-seq over other technologies, we choose RNA-seq as our approach for transcriptome profiling. We sequenced the whole transcriptomes of MC-ir NCs compared with control group to get the key gene terms and pathways in the lineage reprogramming.Methods: MC-irNCs(melanoma cell-induced-resembled neuronal cells) are derived from A375 cell by inducing "forced" overexpression of specific genes: Achaete-scute homolog 1(Ascl1), Neuronal differentiation factor 1(Neurod1), Myelin transcription factor 1(Myt1l), Brain protein 2(Brn2, also called POU3F2) and human brain-derived neurotrophic factor(h-BDNF). To achieve the goal, systems biology approaches were first applied to irNCs collected on 14 th day after infection in different irNCs model. Besides, RT-PCR was performed to checking the results.Result: We successfully reprogrammed A375 cells to MC-irNCs by the Ascl1, Neurod1, Myt1 l, Brn2, h-BDNF. Employing deep sequencing, we sequenced mRNA transcripts among 4-factor group, 5-factor group and control group. There were 893 differentially expressed genes(DEGs) between 4-factor group and control group, so was 512 DEGs between 5-factor group and control group. There were 409 DEGs between 4-factor group and 5-factor group. Among them, cell differentiation and neuronal cell growth were significant. We found the PI3 K and MAPK pathway might contribute to the reprogramming process. Through bioinformatics network construction, IGF-1 was identified as one of the key node gene in different reprogramming protocol.Conclusion: Based on these findings, we thought that PI3 K and MAPK pathway may be a key target in the reprogramming procedure. Overexpression of IGF-1 hold great promise in improving resembled neural cells derived directly from different cell lineage.