In the past few years, investigators have taken LY2109761 700874-71-1 advantage of this opportunity to establish iPSC lines in a variety of neuropsychiatric disorders including Rett Syndrome, Parkinson Disease, Amyotrophic Lateral SJN 2511 Sclerosis, Familial Dysautonomia, and most recently, SZ. In the study reported by Brennand et al. neurons derived from SZ-specific iPSCs showed diminished neuronal connectivity, reduced PSD95-protein levels and altered expression of WNT signaling pathways. Similarly, we have also been developing iPSC lines from patients with SZ, a data set that includes patients with 22q11.2 deletions. In addition to their utility for disease modeling in neuropsychiatric problems, iPSCs can also be used to study early differentiating human neurons in vitro to gain insight into neurogenesis, which is particularly relevant to both SZ and ASD considering that both appear to have a neurodevelopmental basis. With these aspects of disease pathogenesis in mind, we have analyzed the transcriptome of human neurons derived from iPSCs using RNA-Seq, a method that provides increased sensitivity with the capacity to detect low-copy transcripts, novel transcripts, lncRNAs, and splice isoforms. The key role played by cell type-specific splicing in neuronal differentiation, particularly in genes coding for cell adhesion proteins, and the growing recognition that lncRNAs play a role neurogenesis lend further support for the value of deep sequencing transcriptome analysis. Finally, a global, unbiased transcriptome analysis could help determine the biological significance of SNP markers associated with neuropsychiatric disorders identified in GWAS carried out in SZ, ASD, BD, many of which map to intergenic regions or deep within large introns where important regulatory lncRNAs may be found. In this study we show that RNA from a limited sample can be reliably amplified preserving quantitative changes and splice isoform integrity. Several novel findings emerged, including the discovery that lncRNAs that map to the HOXA and HOXB gene loci are expressed early in neurogenesis, and that at least one, HOXAIRM1, is expressed in fetal brain. Considering the effect of HOTAIRM1 on HOXA gene expression and myelopoiesis, our findings suggest a similar role in neurogenesis as well, but that remains to be determined experimentally. Similarly, the two other lncRNAs that map to HOX gene loci, RP11-357H14.12 and AC036222.1, that increase in differentiating neurons are excellent candidates for regulating HOX gene expression in the developing brain. The HOX genes play a role in brain development by determining rhombomere segmental identity, regional neural identity and anterior posterior patterning during early embryogenesis. Most of the work on the role of HOX genes on brain development has been carried out in drosophila and mouse. Using neurons derived from iPSCs will provide an opportunity to study the regulation of these genes, their targets, and their apparent lncRNA regulators in human tissue, in vitro.