Deep RNA-seq of male and female murine sensory neuron subtypes after nerve injury
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ABSTRACT:
PROVIDER: PRJNA893631 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22026100_1.fastq.gz | Fastqsanger.gz | |||
| SRR22026100_2.fastq.gz | Fastqsanger.gz | |||
| SRR22026200_1.fastq.gz | Fastqsanger.gz | |||
| SRR22026200_2.fastq.gz | Fastqsanger.gz | |||
| SRR22026300_1.fastq.gz | Fastqsanger.gz |
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Project description:Primary afferent pathophysiology is thought to be a key driver in painful conditions, with dorsal root ganglia (DRG) neurons being well described for their role in driving both acute and chronic pain. These neurons encompass a diverse collection of subtypes that are grouped by various factors, each intrinsically related. These include size, myelination, conduction velocity, projection patterns, end organs, and general function. More recently, these subpopulations have been well documented through single cell and single nuclear RNA-seq in mice and human. This diversity is lost during bulk RNA-seq, due to the consolidation of all subtypes together. In single cell datasets, pseudo-bulk samples can be generated for each cluster, but this relies on a well-defined clustering that can be lost after nerve injury. As such, changes at a subtype level remain unclear in painful states. Here, we address this gap through the deep transcriptional profiles of multiple murine DRG populations in acute and chronic pain states while considering sex differences. We have studied the molecular changes in five populations: Scn10a-expressing DRG, peptidergic and non-peptidergic nociceptors, as well as C-LTMRs and Ntrk2-expressing A-LTMRs. In a naive state, we find subtype specific sexual dimorphism in a small number of genes. This does not translate to a strong interaction of sex and injury, as the injury response seems to be consistent across sexes at the neuronal transcript level. We also see both stereotypes and unique subpopulation signatures in injured states after nerve injury at both an acute (3 day) and chronic (4 week) timepoint, with notable changes in C-LTMR and NP populations, as well as a distinct transcriptional program in AB-RA + Ad-LTMRs by 4 weeks compared to the other subtypes in the study. This data has been deposited in a searchable database to increase accessibility at https://livedataoxford.shinyapps.io/drg-directory/.
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Project description:AbstractDorsal root ganglia (DRG) neurons have been well described for their role in driving both acute and chronic pain. Although nerve injury is known to cause transcriptional dysregulation, how this differs across neuronal subtypes and the impact of sex is unclear. Here, we study the deep transcriptional profiles of multiple murine DRG populations in early and late pain states while considering sex. We have exploited currently available transgenics to label numerous subpopulations for fluorescent-activated cell sorting and subsequent transcriptomic analysis. Using bulk tissue samples, we are able to circumvent the issues of low transcript coverage and drop-outs seen with single-cell data sets. This increases our power to detect novel and even subtle changes in gene expression within neuronal subtypes and discuss sexual dimorphism at the neuronal subtype level. We have curated this resource into an accessible database for other researchers ( https://livedataoxford.shinyapps.io/drg-directory/ ). We see both stereotyped and unique subtype signatures in injured states after nerve injury at both an early and late timepoint. Although all populations contribute to a general injury signature, subtype enrichment changes can also be seen. Within populations, there is not a strong intersection of sex and injury, but previously unknown sex differences in naïve states-particularly in Aβ-RA + Aδ-low threshold mechanoreceptors-still contribute to differences in injured neurons.
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