Genetic Mechanism Study of Auditory Phoenix Spheres and Transcription Factors Prediction for Direct Reprogramming by Bioinformatics

Background: Hearing loss is the most common irreversible sensory disorder. By delivering regenerative cells into the cochlea, cell-based therapy provides a novel strategy for hearing restoration. Recently, newly-identified phoenix cells have drawn attention due to their nearly unlimited self-renewal and neural differentiation capabilities. They are a promising cell source for cell therapy and a potential substitute for induced pluripotent stem cells (iPSCs) in many in vitro applications. However, the underlying genomic mechanism of their self-renewal capabilities is largely unknown. The aim of this study was to identify hub genes and potential molecular mechanisms between differentiated and undifferentiated phoenix cells and predict transcription factors (TFs) for direct reprogramming. Material and Methods: The datasets were downloaded from the ArrayExpress database. Samples of differentiated and undifferentiated phoenix cells with three biological replicates were utilised for bioinformatic analysis. Differentially expressed genes (DEGs) were screened and the Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were investigated. The gene set enrichment analysis (GSEA) was conducted to verify the enrichment of four self-defined gene set collections, followed by protein-protein interaction (PPI) network construction and subcluster analysis. The prediction of TFs for direct reprogramming was performed based on the TRANSFAC database. Results: Ten hub genes were identified to be the key candidates for self-renewal. Ten TFs were predicted as the direct reprogramming factors. This study provides a theoretical foundation for understanding phoenix cells and clues for direct reprogramming, which would stimulate further experiments and clinical applications in hearing research and treatment.