Selection of neural differentiation-specific genes by comparing profiles of random differentiation

Differentiation of embryonic stem cells (ESCs) into neurons requires a high level of transcriptional regulation. To further understand the transcriptional regulation of neural differentiation of ESCs, we used oligonucleotide microarray to examine the gene expressions of the guided differentiation (GD) model for dopaminergic (DA) neurons from mouse ESCs. We also determined the gene expression profiles of the random differentiation (RD) model of mouse ESCs into embryoid bodies. From K-means clustering analysis using the expression patterns of the two models, most of the genes (1,282 of 1,884 genes [68.0%]) overlapped in their expression patterns. Six hundred twenty-two differentially expressed genes (DEGs) from the GD model by random variance F-test were classified by their critical molecular functions in neurogenesis and DNA replication (Gene Ontology analysis). However, 400 genes among GD-DEGs (64.3%) showed a high correlation with RD in Spearman's correlation analysis (Spearman's coefficient p(s) >or= .6). The genes showing marginal correlation (-.4 < p(s) < .6) were present in the early stages of differentiation of both GD and RD, which were non-specific to brain development. Finally, we distinguished 66 GD-specific genes based on p(s)