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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.

Publication ,  Journal Article
Tansley, S; Uttam, S; Ureña Guzmán, A; Yaqubi, M; Pacis, A; Parisien, M; Deamond, H; Wong, C; Rabau, O; Brown, N; Haglund, L; Ouellet, J ...
Published in: Nat Commun
February 11, 2022

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.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

February 11, 2022

Volume

13

Issue

1

Start / End Page

843

Location

England

Related Subject Headings

  • Spinal Cord
  • Sequence Analysis, RNA
  • Polymorphism, Genetic
  • Peripheral Nerve Injuries
  • Microglia
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Gene Expression
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Tansley, S., Uttam, S., Ureña Guzmán, A., Yaqubi, M., Pacis, A., Parisien, M., … Khoutorsky, A. (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. Nat Commun, 13(1), 843. https://doi.org/10.1038/s41467-022-28473-8
Tansley, Shannon, Sonali Uttam, Alba Ureña Guzmán, Moein Yaqubi, Alain Pacis, Marc Parisien, Haley Deamond, et al. “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.Nat Commun 13, no. 1 (February 11, 2022): 843. https://doi.org/10.1038/s41467-022-28473-8.
Tansley S, Uttam S, Ureña Guzmán A, Yaqubi M, Pacis A, Parisien M, et al. 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. Nat Commun. 2022 Feb 11;13(1):843.
Tansley, Shannon, et al. “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.Nat Commun, vol. 13, no. 1, Feb. 2022, p. 843. Pubmed, doi:10.1038/s41467-022-28473-8.
Tansley S, Uttam S, Ureña Guzmán A, Yaqubi M, Pacis A, Parisien M, Deamond H, Wong C, Rabau O, Brown N, Haglund L, Ouellet J, Santaguida C, Ribeiro-da-Silva A, Tahmasebi S, Prager-Khoutorsky M, Ragoussis J, Zhang J, Salter MW, Diatchenko L, Healy LM, Mogil JS, Khoutorsky A. 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. Nat Commun. 2022 Feb 11;13(1):843.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

February 11, 2022

Volume

13

Issue

1

Start / End Page

843

Location

England

Related Subject Headings

  • Spinal Cord
  • Sequence Analysis, RNA
  • Polymorphism, Genetic
  • Peripheral Nerve Injuries
  • Microglia
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Gene Expression
  • Female