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Chunk #31 — Results — iPSC generation, characterization, and neural differentiation 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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Using classical Yamanaka factors15 (OCT4, SOX2, KLF4 and cMYC) delivered in retroviral vectors, at least three iPSC colonies from each fibroblast line from all four Family-811 quartet members were isolated, expanded, and fully characterized. All 12 iPSC lines were picked from primary iPSC colonies prior to any splitting and were expanded separately and thus can be considered independent iPSCs lines. Karyotype analysis indicated all 12 iPSCs were normal (Sup. Fig. 2), and a 23 SNP marker panel used for fingerprinting iPSCs post-reprogramming corresponded to their respective parental fibroblast lines (data not shown). Pluripotency of all 12 iPSC lines from the quartet was initially assessed through measurement of a panel of characteristic pluripotency markers, including NANOG, OCT4, SSEA-4, Tra-1-60 and Tra-1-81 (Sup. Fig. 3). As a further test of pluripotency, genome-wide transcriptome profiles were generated from all 12 iPSCs and PluriTest, a bioinformatic assay that uses global gene expression profiles to bench mark unknown iPSCs with bona fide pluripotent cells44, was performed. The results of the PluriTest confirmed that the 12 iPSCs were highly similar in their transcriptome to previously described