Single nuclei ATAC-seq (10X Genomics Chromium) of FACS enriched cortical and hippocampal interneurons from P30 mouse brains

While epigenetic modifications are critical for cell state changes throughout development, a detailed characterization of chromatin accessibility during neurogenesis has not been explored. We collected single-cell chromatin accessibility profiles of ~40,000 cells from 4 distinct neurogenic regions of the embryonic mouse forebrain using single nuclei ATAC-Seq (snATAC-Seq). We identified thousands of differentially accessible peaks, many of which were restricted to distinct progenitor cell types or brain regions. By integrating snATAC-Seq and transcriptome data, we characterized changes of chromatin accessibility at enhancers and promoters that were tightly coupled to transcript abundance throughout neurodevelopment. Integrating our chromatin accessibility profiles from embryonic and adult interneurons with the iPSYCH2012 GWAS dataset revealed several disease-associated polymorphisms overlapped accessible regions in embryonic cells and MGE-derived mature interneurons. These findings highlight the coordination between chromatin accessibility and gene expression as neural progenitors mature during embryogenesis, and open the door for future studies to define critical enhancer-promoter interactions that direct cell fate decisions. Overall design: FACS enriched cortical and hippocampal interneuron nuclei from P30 mouse brains. 2 replicates per region.