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

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. Usin...

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Vydáno v:Nature communications Ročník 13; číslo 1; s. 843 - 16
Hlavní autoři: Tansley, Shannon, Uttam, Sonali, Ureña Guzmán, Alba, Yaqubi, Moein, Pacis, Alain, Parisien, Marc, Deamond, Haley, Wong, Calvin, Rabau, Oded, Brown, Nicole, Haglund, Lisbet, Ouellet, Jean, Santaguida, Carlo, Ribeiro-da-Silva, Alfredo, Tahmasebi, Soroush, Prager-Khoutorsky, Masha, Ragoussis, Jiannis, Zhang, Ji, Salter, Michael W., Diatchenko, Luda, Healy, Luke M., Mogil, Jeffrey S., Khoutorsky, Arkady
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Nature Publishing Group UK 11.02.2022
Nature Publishing Group
Nature Portfolio
Témata:
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45
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692/699/375/1692
Animals
Apolipoprotein E
Apolipoproteins E - genetics
Cell Proliferation
Chronic pain
Chronic Pain - genetics
Developmental stages
Female
Gene Expression
Gene sequencing
Humanities and Social Sciences
Hypersensitivity
Inflammation
Injuries
Male
Males
Mice
Mice, Inbred C57BL
Microglia
multidisciplinary
Pain
Peripheral Nerve Injuries
Peripheral nerves
Peripheral neuropathy
Polymorphism, Genetic
Ribonucleic acid
RNA
Science
Science (multidisciplinary)
Sequence analysis
Sequence Analysis, RNA
Sex
Spinal Cord
Spinal cord injuries
Subpopulations
Transcription
ISSN:2041-1723, 2041-1723
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Shrnutí: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. Microglia subpopulations may differentially contribute to pain. Here, the authors show that peripheral nerve injury induces time- and sex-specific transcriptional changes in mouse spinal cord microglia subpopulations and that ApoE is linked to neuropathic pain hypersensitivity in mice and humans.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-022-28473-8