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

Pradipta R. Ray, Jawad Khan, Andi Wangzhou, Diana Tavares-Ferreira, Armen N Akopian, Gregory Dussor, Theodore J. Price

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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 vs. 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.

Original languageEnglish (US)
Article number37
JournalFrontiers in Molecular Neuroscience
Volume12
DOIs
StatePublished - Feb 12 2019

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Tibial Nerve
Gene Expression Profiling
Immunity
Sex Characteristics
Chronic Pain
Inflammation
Peripheral Nervous System
Gene Expression
Pain
Genes
Nervous System Physiological Phenomena
Somatoform Disorders
Neuronal Plasticity
Transcriptome
Neuroglia
Type 2 Diabetes Mellitus
Arthritis
Transcription Factors
Tissue Donors
Databases

Keywords

  • Human peripheral nerve transcriptome
  • Pain genes
  • Peripheral nervous system sex differences
  • Pro-inflammatory genes
  • Sex-differential gene expression

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Transcriptome analysis of the human tibial nerve identifies sexually dimorphic expression of genes involved in pain, inflammation, and neuro-immunity. / Ray, Pradipta R.; Khan, Jawad; Wangzhou, Andi; Tavares-Ferreira, Diana; Akopian, Armen N; Dussor, Gregory; Price, Theodore J.

In: Frontiers in Molecular Neuroscience, Vol. 12, 37, 12.02.2019.

Research output: Contribution to journalArticle

Ray, Pradipta R. ; Khan, Jawad ; Wangzhou, Andi ; Tavares-Ferreira, Diana ; Akopian, Armen N ; Dussor, Gregory ; Price, Theodore J. / Transcriptome analysis of the human tibial nerve identifies sexually dimorphic expression of genes involved in pain, inflammation, and neuro-immunity. In: Frontiers in Molecular Neuroscience. 2019 ; Vol. 12.
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