Single-Nucleus Profiling Identifies Accelerated Oligodendrocyte Precursor Cell Senescence in a Mouse Model of Down Syndrome.

ABSTRACT: Down syndrome (DS), the most common genetic cause of intellectual disability, is associated with lifelong cognitive deficits. However, the mechanisms by which triplication of chromosome 21 genes drive neuroinflammation and cognitive dysfunction are poorly understood. Here, using the Ts65Dn mouse model of DS, we performed an integrated single-nucleus ATAC and RNA-sequencing (snATAC-seq and snRNA-seq) analysis of the adult cortex. We identified cell type-specific transcriptional and chromatin-associated changes in the Ts65Dn cortex, including regulators of neuroinflammation, transcription and translation, myelination, and mitochondrial function. We discovered enrichment of a senescence-associated transcriptional signature in Ts65Dn oligodendrocyte (OL) precursor cells (OPCs) and epigenetic c

SUBMITTER: Rusu B 

PROVIDER: S-EPMC10449487 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature