Molecular neurobiological insight into human nervous tissues is needed to generate next-generation therapeutics for neurological disorders such as chronic pain. We obtained human dorsal root ganglia (hDRG) samples from organ donors and performed RNA-sequencing (RNA-seq) to study the hDRG transcriptional landscape, systematically comparing it with publicly available data from a variety of human and orthologous mouse tissues, including mouse DRG (mDRG). We characterized the hDRG transcriptional profile in terms of tissue-restricted gene coexpression patterns and putative transcriptional regulators, and formulated an information-theoretic framework to quantify DRG enrichment. Relevant gene families and pathways were also analyzed, including transcription factors, G-protein-coupled receptors, and ion channels. Our analyses reveal an hDRG-enriched protein-coding gene set (∼140), some of which have not been described in the context of DRG or pain signaling. Most of these show conserved enrichment in mDRG and were mined for known drug–gene product interactions. Conserved enrichment of the vast majority of transcription factors suggests that the mDRG is a faithful model system for studying hDRG, because of evolutionarily conserved regulatory programs. Comparison of hDRG and tibial nerve transcriptomes suggests trafficking of neuronal mRNA to axons in adult hDRG, and are consistent with studies of axonal transport in rodent sensory neurons. We present our work as an online, searchable repository (https://www.utdallas.edu/bbs/painneurosciencelab/sensoryomics/drgtxome), creating a valuable resource for the community. Our analyses provide insight into DRG biology for guiding development of novel therapeutics and a blueprint for cross-species transcriptomic analyses.
We generated RNA-sequencing data from human dorsal root ganglia samples, analyzed with other human and orthologous mouse tissue transcriptomes, to systematically uncover tissue-restricted genes in human and mouse dorsal root ganglia with implications for sensory biology and pain drug discovery.
aSchool of Behavioral and Brain Sciences, The University of Texas at Dallas, Richardson, TX, USA
bDepartment of Biological Sciences, The University of Texas at Dallas, Richardson, TX, USA
Corresponding author. Address: School of Behavioral and Brain Sciences, The University of Texas at Dallas, BSB 14.102G, 800 W Campbell Rd, Richardson, TX 75080, USA. Tel.: 972-883-4311. E-mail address: firstname.lastname@example.org (T.J. Price).
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The authors declare that this work is original and unpublished. A preprint is uploaded on BioRxiv.
Received October 27, 2017
Received in revised form February 08, 2018
Accepted March 12, 2018