Having observed a neurogenesis deficit from the BD-patient iPSCs, to ensure that that the differentiation deficit did not represent a general differentiation defect of the iPSCs, we turned to an evaluation of the overall differentiation capacity of all 12 of iPSCs from the Family-811 quartet that we had generated. For these measurements, three independent iPSCs lines from each of the unaffected parents (6 lines total) and three independent iPSCs lines from the BD sons were grown (6 lines total) for 16 days under non-directed differentiation conditions and total RNA was isolated. The expression of a panel of 500 genes designed by Bock and colleagues as a “scorecard” to quantitatively define the differentiation capacity of human embryonic stem cell (ESCs)/iPSCs of unknown developmental capacity was then assessed using NanoString digital mRNA expression profiling technology, a highly sensitive, single-molecule imaging of color-coded, molecular barcoded probes (Sup. Table 6)37. Using this scorecard, we found no correlation between an iPSC line’s ability to establish NPCs and its predicted differentiation capacity into ectoderm-derived cell types or the expression of a broad set of endodermal and
