Gene expression profiles in SOX10-deficient human iPS cell-derived neural crest cells

Waardenburg syndrome (WS) is a autosomal dominant inherited disorder characterized by sensorineural hearing loss (SNHL) and pigment abnormalities. SOX10 is one of its main pathogenicity genes. In vitro generation of patient-specific induced pluripotent stem cells (iPSCs) is an effective approach for exploring the mechanisms of human disease. Here, we established an iPSCs from a WS patient with SOX10 mutation and differentiated it into induced neural crest cells (NCCs), the key cell type involves in inner ear development. Compared with control-derived iPSCs, the SOX10 mutant iPSCs showed significantly decreased efficiency of development and differentiation potential at the stage of NCCs. We then performed high-throughput RNA-seq and examined the transcriptional misregulation at each stage. The transcriptome analysis differentiated NCCs reveals widespread gene expression changes and the differentially expressed genes(DEGs) were enriched with gene ontology (GO) of neuron migration, skeletal system development, multicellular organism development, which indicate the important role of SOX10 plays in the differentiation of NCCs. It's worth noting that, a significant enrichment among the nominal DEGs for genes implicated in inner ear development was found, as well as several genes related to the inner ear morphogenesis. Based on protein-protein interaction（PPI）net work, we selected four candidate genes that may be regulated by SOX10 in inner ear development: BMP2, LGR5, GBX2 and GATA3. In conclusion, the SOX10 deficiency in this WS patient has a significant impact on the gene expression patterns during the development of NCCs. The DEGs most significantly enriched the inner ear development and morphogenesis could help explain the underlying basis for the inner ear malformation seen in WS patient. Gene expression profiles were compared between wild type iPS cell-derived neural crest cells and SOX10 mutant iPS cell-derived neural crest cells