Aberrant medial ganglionic eminence (MGE) GABAergic neurogenesis contributes to Huntington’s disease pathogenesis

This study used single-cell RNA sequencing to characterize early transcriptional alterations in medial ganglionic eminence (MGE) development caused by mutant huntingtin expression in a Huntington’s disease mouse model. Single-cell transcriptomes were generated from fluorescence-activated cell sorted (FACS) Dlx1-eGFP–positive MGE cells isolated from embryonic day 12.5 (E12.5) BACHD and wild-type control embryos. To control for biological variability, MGE tissue from eight embryos per genotype was collected and pooled into two independent biological replicates per condition, with each replicate consisting of four paired MGEs. Following dissociation and sorting, each replicate was processed independently for single-cell library preparation using the Chromium Next GEM Single Cell 3′ v3.1 platform (10x Genomics). Libraries were sequenced on an Illumina NextSeq 2000, yielding an average depth of approximately 26,000 reads per cell. Single-cell transcriptomic profiling was used to (i) resolve the cellular composition of the E12.5 MGE, (ii) define major progenitor and precursor populations along the MGE neurogenic trajectory, and (iii) assess genotype-dependent transcriptional changes using pseudobulk differential expression approaches. Particular emphasis was placed on basal GABAergic progenitors and postmitotic precursor cells. Together, this scRNA-seq dataset provides a high-resolution framework for interrogating how mutant huntingtin perturbs early progenitor states and downstream lineage programs during ventral telencephalic development, particularly the MGE.