Single‐Cell Transcriptome Meta‐Analysis Reveals Epigenomic and Chromatin Dysregulation in Developing Neurons Derived From Human <scp>ESCs</scp> With 1q21.1 <scp>CNVs</scp>

Recent efforts to construct disease-specific multimodal omics databases at single-cell resolution, along with advances in reconstructive technologies such as brain organoids, have opened up opportunities to elucidate the molecular basis of complex human neuropsychiatric diseases. In this study, we performed a meta-analysis to characterize disease-associated regulatory modules by performing single-cell transcriptome analysis of developing neurons from reciprocal human ESC models of CNV in the distal 1q21.1 region. As a result, we observed significant directional enrichment of a series of genes in neuronal cells associated with autism spectrum disorder (ASD), bipolar disorder, and schizophrenia. Correlation analyses revealed that the disease-associated signature primarily targeted epigenetic regulatory mechanisms. We also identified Bromodomain PHD Finger Transcription Factor (BPTF), a key component of the NURF chromatin remodeling complex, as a potential target responsible for transcriptome changes related to human neuropsychiatric diseases, including ASD. We provide a practical and straightforward analytical workflow for utilizing both public data and in-house single-cell omics data from disease models.