Allele-specific open chromatin in human neurons elucidates functional noncoding disease variants

ASoC variants are prevalent and cell type-specific ASoC variants were over-represented in intergenic regions and active enhancers. The collection includes ATAC-Seq and RNA-Seq data that were taken from human iPS cells and their derived neuronal cells (neural progenitor cells, cortical glutamatergic neurons, GABAergic neurons, and dopaminergic neurons). In order to detect the changes in chromatin accessibility as well as associated changes at the transcriptional level during neuronal differentiation, we applied human induced pluripotent stem cells (hiPSCs) and hiPSC-derived neurons as a neurodevelopmental model. Generally, 8 iPSC lines from RUCDR were induced to differentiate into neural progenitor cells (NPC), 15-day cortical glutamatergic neurons (CN, Glut d15), GABAergic neurons, and dopaminergic neurons. Their open chromatin landscape, as well as transcriptional activities, were measured using ATAC-Seq and bulk RNA-Seq, respectively. An additional 12 lines were used to generate NPC cells and Glut-d15 neurons for ATAC-Seq, with the aim in gaining extended statistic power for ASoC analysis.