Mapping the glial transcriptome in Huntington's disease using snRNAseq: selective disruption of glial signatures across brain regions.

ABSTRACT: Huntington's disease (HD) is an autosomal dominant neurodegenerative disease with a fatal outcome. There is accumulating evidence of a prominent role of glia in the pathology of HD, and we investigated this by conducting single nuclear RNA sequencing (snRNAseq) of human post mortem brain in four differentially affected regions; caudate nucleus, frontal cortex, hippocampus and cerebellum. Across 127,205 nuclei from donors with HD and age/sex matched controls, we found heterogeneity of glia which is altered in HD. We describe prominent changes in the abundance of certain subtypes of astrocytes, microglia, oligodendrocyte precursor cells and oligodendrocytes between HD and control samples, and these differences are widespread across brain regions. Furthermore, we highlight possible mechanisms

SUBMITTER: Bostrand SMK 

PROVIDER: S-EPMC11492505 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature