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Brief Research Report ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Mol. Neurosci. | doi: 10.3389/fnmol.2019.00037

Transcriptome analysis of the human tibial nerve identifies sexually dimorphic expression of genes involved in pain, inflammation and neuro-immunity

  • 1School of Behavioral and Brain Sciences, The University of Texas at Dallas, United States
  • 2The University of Texas Health Science Center at San Antonio, United States

Sex differences in gene expression are important contributors to normal physiology and mechanisms of disease. This is increasingly apparent in understanding and potentially treating chronic pain where molecular mechanisms driving sex differences in neuronal plasticity are giving new insight into why certain chronic pain disorders preferentially affect women versus men. Large transcriptomic resources are now available and can be used to mine for sex differences to gather insight from molecular profiles using donor cohorts. We performed in-depth analysis of 248 human tibial nerve (hTN) transcriptomes from the GTEx Consortium project to gain insight into sex-dependent gene expression in the peripheral nervous system (PNS). We discover 149 genes with sex differential gene expression. Many of the more abundant genes in men are associated with inflammation and appear to be primarily expressed by glia or immune cells, with some genes downstream of Notch signaling. In women, we find the differentially expressed transcription factor SP4 that is known to drive a regulatory program, and may impact sex differences in PNS physiology. Many of these 149 differentially expressed (DE) genes have some previous association with chronic pain but few of them have been explored thoroughly. Additionally, using clinical data in the GTEx database, we identify a subset of DE, sexually dimorphic genes in diseases associated with chronic pain: arthritis and type II diabetes. Our work creates a unique resource that identifies sexually dimorphic gene expression in the human PNS with implications for discovery of sex-specific pain mechanisms.

Keywords: Sex-differential gene expression, Human peripheral nerve transcriptome, Peripheral Nervous System sex differences, pain genes, pro-inflammatory genes

Received: 26 Oct 2018; Accepted: 31 Jan 2019.

Edited by:

Guilherme Lucas, University of São Paulo, Brazil

Reviewed by:

Alexandre Henriques, Neuro-Sys, France
Sangsu Bang, Duke University, United States  

Copyright: © 2019 Ray, Kahn, Wangzhou, Tavares-Ferreira, Akopian, Dussor and Price. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Theodore J. Price, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Richardson, 75080-3021, Texas, United States, Theodore.Price@utdallas.edu