Temporal single-cell atlas of full-length Huntington's disease mouse model defines stage-specific signatures of corticostriatal dysfunction.

ABSTRACT: Huntington's disease involves progressive corticostriatal dysfunction; however, the timing of region-specific transcriptional changes remains unresolved at cellular resolution. Here, we provide a temporal single-nucleus transcriptomic atlas of striatum and motor cortex from zQ175 knock-in mice at 6 and 18 months. This full-length Huntingtin model enables staging of progressive circuit dysfunction. Striatal projection neurons show extensive early dysregulation with progressive striosomal identity erosion, whereas cortical pyramidal neuron dysfunction was layer-specific and coincided with motor symptom onset. By modeling genotype-dependent effects, we distinguish region- and cell type-specific signatures of core disease mechanisms from age-related changes and compensatory adaptations. Integr

SUBMITTER: Robbins AB 

PROVIDER: S-EPMC12803248 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature