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Chunk #40 — Results — NanoString molecular profiling of iPSCs, NPCs and neurons from Family-811

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Characterization of bipolar disorder patient-specific induced pluripotent stem cells from a family reveals neurodevelopmental and mRNA expression abnormalities.
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To better delineate the phenotypic defects in the BD patient cell lines from the Family-811 quartet, we then examined the average differences in gene expression of the BD patient cells relative to the unaffected parental control cells using the PsychGene NanoString probe set. Starting with the fibroblasts, examination of volcano plots in which the Log2(fold change) was plotted against the −Log10(p-value) revealed that only one gene, ZIC1 (ZIC family member 1), a C2H2-type zinc finger transcription factor, met the criteria for a significant expression difference (fold change = 13.3, p-value = 0.04, Benjamini-Hochberg corrected) (Fig. 4C). For iPSCs, there were no genes that exhibited a significant difference in expression between the six control lines and 6 BD patient lines. In sharp contrast to the lack of multiple differentially expressed genes in the fibroblasts and iPSC cell states, when comparing the expression profiles of the FACS-purified NPCs there were 18 genes with significant expression differences between BD-patient NPCs relative to unaffected parental control NPCs (> 1.5 fold change; p-value < 0.05, Benjamini-Hochberg corrected) (Fig. 4C; Fig. 5A). Amongst this set of