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Single-cell RNA sequencing reveals time- and sex-specific responses of mouse spinal cord microglia to peripheral nerve injury and links ApoE to chronic pain

Author

Listed:
  • Shannon Tansley

    (McGill University
    McGill University)

  • Sonali Uttam

    (McGill University)

  • Alba Ureña Guzmán

    (McGill University)

  • Moein Yaqubi

    (McGill University)

  • Alain Pacis

    (Canadian Centre for Computational Genomics, McGill Genome Centre)

  • Marc Parisien

    (McGill University
    McGill University)

  • Haley Deamond

    (McGill University)

  • Calvin Wong

    (McGill University)

  • Oded Rabau

    (McGill University)

  • Nicole Brown

    (McGill University)

  • Lisbet Haglund

    (McGill University)

  • Jean Ouellet

    (McGill University)

  • Carlo Santaguida

    (Montreal Neurological Institute, McGill University)

  • Alfredo Ribeiro-da-Silva

    (McGill University
    McGill University)

  • Soroush Tahmasebi

    (University of Illinois at Chicago)

  • Masha Prager-Khoutorsky

    (McGill University)

  • Jiannis Ragoussis

    (McGill University
    McGill University Genome Centre)

  • Ji Zhang

    (McGill University
    McGill University)

  • Michael W. Salter

    (University of Toronto)

  • Luda Diatchenko

    (McGill University
    McGill University)

  • Luke M. Healy

    (McGill University)

  • Jeffrey S. Mogil

    (McGill University
    McGill University
    McGill University)

  • Arkady Khoutorsky

    (McGill University
    McGill University)

Abstract

Activation of microglia in the spinal cord following peripheral nerve injury is critical for the development of long-lasting pain hypersensitivity. However, it remains unclear whether distinct microglia subpopulations or states contribute to different stages of pain development and maintenance. Using single-cell RNA-sequencing, we show that peripheral nerve injury induces the generation of a male-specific inflammatory microglia subtype, and demonstrate increased proliferation of microglia in male as compared to female mice. We also show time- and sex-specific transcriptional changes in different microglial subpopulations following peripheral nerve injury. Apolipoprotein E (Apoe) is the top upregulated gene in spinal cord microglia at chronic time points after peripheral nerve injury in mice. Furthermore, polymorphisms in the APOE gene in humans are associated with chronic pain. Single-cell RNA sequencing analysis of human spinal cord microglia reveals a subpopulation with a disease-related transcriptional signature. Our data provide a detailed analysis of transcriptional states of mouse and human spinal cord microglia, and identify a link between ApoE and chronic pain in humans.

Suggested Citation

  • Shannon Tansley & Sonali Uttam & Alba Ureña Guzmán & Moein Yaqubi & Alain Pacis & Marc Parisien & Haley Deamond & Calvin Wong & Oded Rabau & Nicole Brown & Lisbet Haglund & Jean Ouellet & Carlo Santag, 2022. "Single-cell RNA sequencing reveals time- and sex-specific responses of mouse spinal cord microglia to peripheral nerve injury and links ApoE to chronic pain," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28473-8
    DOI: 10.1038/s41467-022-28473-8
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    References listed on IDEAS

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