Integrated analyses reveal evolutionarily conserved and specific injury response genes in dorsal root ganglion

Abstract

Rodent dorsal root ganglion (DRG) is widely used for studying axonal injury. Extensive studies have explored genome-wide profiles on rodent DRGs under peripheral nerve insults. However, systematic integration and exploration of these data still be limited. Herein, we re-analyzed 21 RNA-seq datasets and presented a web-based resource (DRGProfile). We identified 53 evolutionarily conserved injury response genes, including well-known injury genes (Atf3, Npy and Gal) and less-studied transcriptional factors (Arid5a, Csrnp1, Zfp367). Notably, we identified species-preference injury response candidates (e.g. Gpr151, Lipn, Anxa10 in mice; Crisp3, Csrp3, Vip, Hamp in rats). Temporal profile analysis reveals expression patterns of genes related to pre-regenerative and regenerating states. Finally, we found a large sex difference in response to sciatic nerve injury, and identified four male-specific markers (Uty, Eif2s3y, Kdm5d, Ddx3y) expressed in DRG. Our study provides a comprehensive integrated landscape for expression change in DRG upon injury which will greatly contribute to the neuroscience community.

Injury distance limits the transcriptional response to spinal injury

“…In contrast, many hundreds or thousands of transcripts typically surpass the same threshold following axotomy in other neuronal cell types (see Fig. 6 below and 10–12,16 ). Comparisons performed population-by-population also revealed few injury-regulated transcripts ( Sup.…”

“…Clarifying the various transcriptional responses to injury is a powerful means to develop strategies to protect vulnerable cell types and to identify both pro-and anti-growth pathways that can be targeted to spur regeneration. These efforts rely on a detailed and accurate description of the baseline injury response and thus a major effort in regenerative neuroscience has been to profile the transcriptional reaction of neurons to axon damage [9][10][11][12][13][14][15] For some cell types, notably sensory neurons of the dorsal root ganglia (DRG) 10,[15][16][17] and retinal ganglion cells (RGCs) 11,12,18,19 , numerous profiling efforts have provided deep insight. In both cell types, work using bulk and single-cell or single-nuclei sequencing has detected many hundreds to thousands of strongly differentially expressed genes (DEGs) after injury [10][11][12]16,18 .…”

“…These efforts rely on a detailed and accurate description of the baseline injury response and thus a major effort in regenerative neuroscience has been to profile the transcriptional reaction of neurons to axon damage [9][10][11][12][13][14][15] For some cell types, notably sensory neurons of the dorsal root ganglia (DRG) 10,[15][16][17] and retinal ganglion cells (RGCs) 11,12,18,19 , numerous profiling efforts have provided deep insight. In both cell types, work using bulk and single-cell or single-nuclei sequencing has detected many hundreds to thousands of strongly differentially expressed genes (DEGs) after injury [10][11][12]16,18 . DRG neurons, which survive axotomy and mount an effective regenerative response, respond to injury with a partial loss of transcripts that distinguish subtypes and the upregulation of numerous transcripts that support axon growth .…”

NGenomeSyn: an easy-to-use and flexible tool for publication-ready visualization of syntenic relationships across multiple genomes

“…The NGenomeSyn has already been applied in visualizing genomic or non-genomic relationships in several research studies ( Guan et al , 2022 ; Hou et al , 2022 ; Xu et al , 2022 ; Yin et al , 2023 ). Given its high flexibility and customization, we believe that NGenomeSyn visualization will help researchers to efficiently explore their data and draw publication-quality figures, specifically for those users without advanced computer skills.…”