-OFF human embryonic stem cells (hESCs) displayed different transcriptome profiles, particularly in genes related to neural lineage. (A) In total, 114 genes displayed significant differential expression between MEG3-ON and MEG3-OFF hESCs. The embryoid body (EB) sample differentiated from ‘MEG3-ON’ hESCs was used as a reference for differentiated hESCs. The heatmap represents the most significant differentially expressed genes selected by the intersection indicated by Welch’s t test (P <0.05; fold change >1.5) and significance analysis of microarrays (SAM) (false discovery rate <0.05). The heatmap displays differentially expressed genes that can be used to distinguish between the MEG3-ON and MEG3-OFF cell states. The green-to-red colors of the heatmap are linearly mapped to the Z-scores, which range from −3 to 3. (B)
MEG3-ON and MEG3-OFF hESCs showed differences in the expression levels of many genes that correlate with neural lineage development and with different tumor types. This analysis was performed by using MetaCore software (GeneGo), which includes developmental processes 1,317 Gene Ontology (GO) terms in Biological Process for GO process testing and literature-based biomarkers of clinical diseases for GO disease testing. (C) A partial gene list of subset of genes related to ‘nervous system development (GO:0007399)’ was clearly shown to be differentially expressed between undifferentiated MEG3-ON and MEG3-OFF hESCs by using GSEA. In this heatmap, expression values are represented as colors, with the range of colors (red, pink, light blue, and dark blue) indicating the range of expression values (high, moderate, low, and lowest, respectively). MEG3, maternally expressed gene 3.