Single cell RNAseq analysis of dorsal root ganglia from global and cLTMR-specific Nav1.7 knockout mice

We investigated changes in gene expression and cell type abundance using single cell RNA sequencing of dorsal root ganglia (DRG) isolated from global (pCAGG-CreER x Nav1.7 floxed) and C-low threshold mechanoreceptor (cLTMR)-specific (Slc17a8-Cre x Nav1.7 floxed) Nav1.7 knockout mice. We identified a reduction in the fraction of cLTMRs and a concomitant emergence of a distinct cell cluster located closely to cLTMRs in the UMAP projection in global Nav1.7 knockout DRGs. This novel cell cluster expressed previously described cLTMR markers with distinct gene expression changes such as a downregulation of Ceacam10 and an upregulation of Penk expression. We further found that cLTMR-specifc knockout of Nav1.7 induced the same shift in cLTMR cells to a knockout-specific cluster with upregulated Penk expression. Overall design: Single cell RNAseq libraries were prepared from lumbar DRGs (L4,5,6) isolated bilaterally from adult, global Nav1.7 knockout (CreER+, N = 7) and littermate controls (CreER-, N = 5) 4 week post-tamoxifen dosing. scRNAseq libraries were also prepared from lumbar DRGs isolated from adult cLTMR-specific Nav1.7 knockout (N = 2) and littermate controls (N = 2).