The current investigation demonstrates that iPSC from BP patients are similar to controls (C) in their tri-lineage differentiation capacity and gene expression profiles; however, the expression of membrane receptors and ion channel transcripts was significantly increased in BP neurons, and different sets of neuronal lineage-specific transcription factors were induced. Consistent with changes in membrane composition, exposure of BP neurons to lithium produced significant alterations in wave amplitude and calcium transient compared with control neurons. Transcripts involved in dorsal telencephalic fate (the default identity) were enriched in control neurons, whereas there was an increase in genes involved in ventral fate and GABAergic interneuron differentiation in BP neurons. The dorsal/ventral neuronal identity of both groups could be influenced by exposure of iPSC to dorsalizing or ventralizing factors. This work provides the first information on gene expression during neuronal differentiation in BP, a rich resource to identify alterations in the differentiation of glia and neurons, as well as an opportunity for comparisons with other neuropsychiatric disorders.
