Ryan G Lim, Osama Al-Dalahmah, Jie Wu, Maxwell P Gold, Jack C Reidling, Guomei Tang, Miriam Adam, David K Dansu, Hye-Jin Park, Patrizia Casaccia, Ricardo Miramontes, Andrea M Reyes-Ortiz, Alice Lau, Richard A Hickman, Fatima Khan, Fahad Paryani, Alice Tang, Kenneth Ofori, Emily Miyoshi, Neethu Michael, Nicolette McClure, Xena E Flowers, Jean Paul Vonsattel, Shawn Davidson, Vilas Menon, Vivek Swarup, Ernest Fraenkel, James E Goldman, Leslie M Thompson
The complexity of affected brain regions and cell types is a challenge for Huntington's disease (HD) treatment. Here we use single nucleus RNA sequencing to investigate molecular pathology in the cortex and striatum from R6/2 mice and human HD post-mortem tissue. We identify cell type-specific and -agnostic signatures suggesting oligodendrocytes (OLs) and oligodendrocyte precursors (OPCs) are arrested in intermediate maturation states. OL-lineage regulators OLIG1 and OLIG2 are negatively correlated with CAG length in human OPCs, and ATACseq analysis of HD mouse NeuN-negative cells shows decreased accessibility regulated by OL maturation genes...
December 21, 2022: Nature Communications