Cell type resolved Micro-C maps from human middle temporal gyrus in Parkinson's disease and control brains
Parkinson's disease (PD) is a common neurodegenerative disorder in which much of the genetic risk resides in the noncoding genome. To characterize the three-dimensional chromatin architecture underlying cell type-specific gene regulation in PD, we generated high-resolution Micro-C chromatin conformation maps from post-mortem human brain tissue. Nuclei were isolated from the middle temporal gyrus of 36 individuals with PD exhibiting neocortical Lewy body pathology and 21 neurologically normal control donors. Fluorescence-activated nuclei sorting was used to purify four major brain cell classes: neurons, oligodendrocytes, astrocytes, and microglia. Low-yield populations were processed in parallel across two instruments, and biological and technical replicates were generated for each cell type. Sorted nuclei were processed using the Dovetail Genomics Micro-C platform to produce nucleosome-resolution chromatin contact maps. These data provide cell type-specific profiles of chromatin loops, topologically associating domains, and fine-scale regulatory interactions in the human cortex.The Micro-C dataset is part of a larger single-nucleus multi-omic study integrating chromatin accessibility, gene expression, quantitative trait locus mapping, and machine learning based variant effect prediction to link rare noncoding variants to regulatory elements and target genes in PD-relevant cell types.