In:
GigaScience, Oxford University Press (OUP), Vol. 12 ( 2022-12-28)
Abstract:
The basal ganglia are a complex of interconnected subcortical structures located beneath the mammalian cerebral cortex. The degeneration of dopaminergic neurons in the basal ganglia is the primary pathological feature of Parkinson's disease. Due to a lack of integrated analysis of multiomics datasets across multiple basal ganglia brain regions, very little is known about the regulatory mechanisms of this area. Findings We utilized high-throughput transcriptomic and epigenomic analysis to profile over 270,000 single-nucleus cells to create a cellular atlas of the basal ganglia, characterizing the cellular composition of 4 regions of basal ganglia in adult macaque brain, including the striatum, substantia nigra (SN), globus pallidum, and amygdala. We found a distinct epigenetic regulation on gene expression of neuronal and nonneuronal cells across regions in basal ganglia. We identified a cluster of SN-specific astrocytes associated with neurodegenerative diseases and further explored the conserved and primate-specific transcriptomics in SN cell types across human, macaque, and mouse. Finally, we integrated our epigenetic landscape of basal ganglia cells with human disease heritability and identified a regulatory module consisting of candidate cis-regulatory elements that are specific to medium spiny neurons and associated with schizophrenia. Conclusions In general, our macaque basal ganglia atlas provides valuable insights into the comprehensive transcriptome and epigenome of the most important and populous cell populations in the macaque basal ganglia. We have identified 49 cell types based on transcriptomic profiles and 47 cell types based on epigenomic profiles, some of which exhibit region specificity, and characterized the molecular relationships underlying these brain regions.
Type of Medium:
Online Resource
ISSN:
2047-217X
DOI:
10.1093/gigascience/giad095
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2022
detail.hit.zdb_id:
2708999-X
