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The temporal and spatial signature of microglial transcriptome in neuropathic pain

Microglial activation following peripheral nerve injury is crucial for neuropathic pain (NP) development; however, studies on time-specific and spatial characteristics of microglial transcriptome are scarce. Firstly, we comparatively analysed microglial transcriptome of different brain regions and m...

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Autores principales: Liu, Zeyuan, Liu, Yuzhou, Dai, Junxi, Lao, Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10065820/
https://www.ncbi.nlm.nih.gov/pubmed/36966811
http://dx.doi.org/10.1097/WNR.0000000000001899
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author Liu, Zeyuan
Liu, Yuzhou
Dai, Junxi
Lao, Jie
author_facet Liu, Zeyuan
Liu, Yuzhou
Dai, Junxi
Lao, Jie
author_sort Liu, Zeyuan
collection PubMed
description Microglial activation following peripheral nerve injury is crucial for neuropathic pain (NP) development; however, studies on time-specific and spatial characteristics of microglial transcriptome are scarce. Firstly, we comparatively analysed microglial transcriptome of different brain regions and multiple timepoints after nerve injury by analysing the gene expression profile of GSE180627 and GSE117320. Then, we performed a mechanical pain hypersensitivity test on 12 rat neuropathic pain models using von Frey fibres at various timepoints after nerve injury. To further explore the key gene clusters closely related to the neuropathic pain phenotype, we conducted a weighted gene co-expression network analysis (WGCNA) on the GSE60670 gene expression profile. Lastly, we performed a single-cell sequencing analysis on GSE162807 for identifying microglia subpopulations. We found that the trend of microglia’s transcriptome changes after nerve injury was that mRNA expression changes mainly occur early after injury, which is also consistent with phenotypic changes (NP progression). We also revealed that in addition to spatial specificity, microglia are also temporally specific in NP progression following nerve injury. The WGCNA findings revealed that the functional analysis of the key module genes emphasized the endoplasmic reticulum’s (ER’s) crucial role in NP. In our single-cell sequencing analysis, microglia were clustered into 18 cell subsets, of which we identified specific subsets of two timepoints (D3/D7) post-injury. Our study further revealed the temporal and spatial gene expression specificity of microglia in neuropathic pain. These results contribute to our comprehensive understanding of the pathogenic mechanism of microglia in neuropathic pain.
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spelling pubmed-100658202023-04-01 The temporal and spatial signature of microglial transcriptome in neuropathic pain Liu, Zeyuan Liu, Yuzhou Dai, Junxi Lao, Jie Neuroreport Cellular, Molecular and Developmental Neuroscience Microglial activation following peripheral nerve injury is crucial for neuropathic pain (NP) development; however, studies on time-specific and spatial characteristics of microglial transcriptome are scarce. Firstly, we comparatively analysed microglial transcriptome of different brain regions and multiple timepoints after nerve injury by analysing the gene expression profile of GSE180627 and GSE117320. Then, we performed a mechanical pain hypersensitivity test on 12 rat neuropathic pain models using von Frey fibres at various timepoints after nerve injury. To further explore the key gene clusters closely related to the neuropathic pain phenotype, we conducted a weighted gene co-expression network analysis (WGCNA) on the GSE60670 gene expression profile. Lastly, we performed a single-cell sequencing analysis on GSE162807 for identifying microglia subpopulations. We found that the trend of microglia’s transcriptome changes after nerve injury was that mRNA expression changes mainly occur early after injury, which is also consistent with phenotypic changes (NP progression). We also revealed that in addition to spatial specificity, microglia are also temporally specific in NP progression following nerve injury. The WGCNA findings revealed that the functional analysis of the key module genes emphasized the endoplasmic reticulum’s (ER’s) crucial role in NP. In our single-cell sequencing analysis, microglia were clustered into 18 cell subsets, of which we identified specific subsets of two timepoints (D3/D7) post-injury. Our study further revealed the temporal and spatial gene expression specificity of microglia in neuropathic pain. These results contribute to our comprehensive understanding of the pathogenic mechanism of microglia in neuropathic pain. Lippincott Williams & Wilkins 2023-04-05 2023-03-20 /pmc/articles/PMC10065820/ /pubmed/36966811 http://dx.doi.org/10.1097/WNR.0000000000001899 Text en Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Cellular, Molecular and Developmental Neuroscience
Liu, Zeyuan
Liu, Yuzhou
Dai, Junxi
Lao, Jie
The temporal and spatial signature of microglial transcriptome in neuropathic pain
title The temporal and spatial signature of microglial transcriptome in neuropathic pain
title_full The temporal and spatial signature of microglial transcriptome in neuropathic pain
title_fullStr The temporal and spatial signature of microglial transcriptome in neuropathic pain
title_full_unstemmed The temporal and spatial signature of microglial transcriptome in neuropathic pain
title_short The temporal and spatial signature of microglial transcriptome in neuropathic pain
title_sort temporal and spatial signature of microglial transcriptome in neuropathic pain
topic Cellular, Molecular and Developmental Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10065820/
https://www.ncbi.nlm.nih.gov/pubmed/36966811
http://dx.doi.org/10.1097/WNR.0000000000001899
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