Fig. 3
Translatome analysis with RiboTag reveals cell type-specific responses in HD. A HdhQ7/Q200 mice homozygous for RiboTag were crossed with homozygous Cre-driver lines to facilitate cell type-specific expression of Rpl22-HA in glutamatergic (vGluT2+) and GABAergic (Gad2+) neurons in the cerebellum and cerebrum, and parvalbumin (PV+)-expressing neurons in the cerebrum. Cerebellum and cerebrum (without olfactory bulb) were separated and flash frozen at 9 months. For RiboTag IPs, cell type-specific HA-tagged ribosomes were immunoprecipitated from tissue homogenate using anti-HA antibody bound to magnetic beads. Total RNA was prepared from an aliquot of the same tissue homogenate. B Expression levels of Htt mRNA were slightly reduced in all cell types, significantly in cerebral vGluT2+ and PV+ neurons (* FDR ≤ 0.05; ** FDR ≤ 0.01; *** FDR ≤ 0.001). C HD-typical genes showed downregulation in cerebral cell types. D Differentially expressed genes (DEGs) (FDR ≤ 0.05) for each cell type. E Top five significantly enriched terms (FDR ≤ 0.05) among DEGs reveal cell type-specific responses to mHtt