Since we noted that a number of the genes were differentially expressed in both BD patients CXCR4+ NPCs and their differentiated neuronal progeny, in order to obtain a global view of the patterns of gene expression we used agglomerative hierarchical clustering to analyze a binary matrix of the total set of 53 significantly dysregulated genes. As shown in Figure 5C, a total of eight categories of genes were identified, including those such as SYN1, SCN2A, CNTN6, and NKX2.2 that were upregulated in both cell states, as well as genes with opposite patterns of expression, such as PAX6, DCX, PLZF that were downregulated in NPCs, but upregulated in neurons. Given that the latter three genes are all considered markers of neural progenitors, these data support the notion of the altered neurodevelopment upon directed differentiation of BD iPSCs.
