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Combination of single-nucleus and bulk RNA-seq reveals the molecular mechanism of thalamus haemorrhage-induced central poststroke pain

Central poststroke pain (CPSP) induced by thalamic haemorrhage (TH) can be continuous or intermittent and is accompanied by paresthesia, which seriously affects patient quality of life. Advanced insights into CPSP mechanisms and therapeutic strategies require a deeper understanding of the molecular...

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Autores principales: Huang, Tianfeng, Xiao, Yinggang, Zhang, Yang, Ge, Yali, Gao, Ju
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10157064/
https://www.ncbi.nlm.nih.gov/pubmed/37153564
http://dx.doi.org/10.3389/fimmu.2023.1174008
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author Huang, Tianfeng
Xiao, Yinggang
Zhang, Yang
Ge, Yali
Gao, Ju
author_facet Huang, Tianfeng
Xiao, Yinggang
Zhang, Yang
Ge, Yali
Gao, Ju
author_sort Huang, Tianfeng
collection PubMed
description Central poststroke pain (CPSP) induced by thalamic haemorrhage (TH) can be continuous or intermittent and is accompanied by paresthesia, which seriously affects patient quality of life. Advanced insights into CPSP mechanisms and therapeutic strategies require a deeper understanding of the molecular processes of the thalamus. Here, using single-nucleus RNA sequencing (snRNA-seq), we sequenced the transcriptomes of 32332 brain cells, which revealed a total of four major cell types within the four thalamic samples from mice. Compared with the control group, the experimental group possessed the higher sensitivity to mechanical, thermal, and cold stimuli, and increased microglia numbers and decreased neuron numbers. We analysed a collection of differentially expressed genes and neuronal marker genes obtained from bulk RNA sequencing (bulk RNA-seq) data and found that Apoe, Abca1, and Hexb were key genes verified by immunofluorescence (IF). Immune infiltration analysis found that these key genes were closely related to macrophages, T cells, related chemokines, immune stimulators and receptors. Gene Ontology (GO) enrichment analysis also showed that the key genes were enriched in biological processes such as protein export from nucleus and protein sumoylation. In summary, using large-scale snRNA-seq, we have defined the transcriptional and cellular diversity in the brain after TH. Our identification of discrete cell types and differentially expressed genes within the thalamus can facilitate the development of new CPSP therapeutics.
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spelling pubmed-101570642023-05-05 Combination of single-nucleus and bulk RNA-seq reveals the molecular mechanism of thalamus haemorrhage-induced central poststroke pain Huang, Tianfeng Xiao, Yinggang Zhang, Yang Ge, Yali Gao, Ju Front Immunol Immunology Central poststroke pain (CPSP) induced by thalamic haemorrhage (TH) can be continuous or intermittent and is accompanied by paresthesia, which seriously affects patient quality of life. Advanced insights into CPSP mechanisms and therapeutic strategies require a deeper understanding of the molecular processes of the thalamus. Here, using single-nucleus RNA sequencing (snRNA-seq), we sequenced the transcriptomes of 32332 brain cells, which revealed a total of four major cell types within the four thalamic samples from mice. Compared with the control group, the experimental group possessed the higher sensitivity to mechanical, thermal, and cold stimuli, and increased microglia numbers and decreased neuron numbers. We analysed a collection of differentially expressed genes and neuronal marker genes obtained from bulk RNA sequencing (bulk RNA-seq) data and found that Apoe, Abca1, and Hexb were key genes verified by immunofluorescence (IF). Immune infiltration analysis found that these key genes were closely related to macrophages, T cells, related chemokines, immune stimulators and receptors. Gene Ontology (GO) enrichment analysis also showed that the key genes were enriched in biological processes such as protein export from nucleus and protein sumoylation. In summary, using large-scale snRNA-seq, we have defined the transcriptional and cellular diversity in the brain after TH. Our identification of discrete cell types and differentially expressed genes within the thalamus can facilitate the development of new CPSP therapeutics. Frontiers Media S.A. 2023-04-20 /pmc/articles/PMC10157064/ /pubmed/37153564 http://dx.doi.org/10.3389/fimmu.2023.1174008 Text en Copyright © 2023 Huang, Xiao, Zhang, Ge and Gao https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Huang, Tianfeng
Xiao, Yinggang
Zhang, Yang
Ge, Yali
Gao, Ju
Combination of single-nucleus and bulk RNA-seq reveals the molecular mechanism of thalamus haemorrhage-induced central poststroke pain
title Combination of single-nucleus and bulk RNA-seq reveals the molecular mechanism of thalamus haemorrhage-induced central poststroke pain
title_full Combination of single-nucleus and bulk RNA-seq reveals the molecular mechanism of thalamus haemorrhage-induced central poststroke pain
title_fullStr Combination of single-nucleus and bulk RNA-seq reveals the molecular mechanism of thalamus haemorrhage-induced central poststroke pain
title_full_unstemmed Combination of single-nucleus and bulk RNA-seq reveals the molecular mechanism of thalamus haemorrhage-induced central poststroke pain
title_short Combination of single-nucleus and bulk RNA-seq reveals the molecular mechanism of thalamus haemorrhage-induced central poststroke pain
title_sort combination of single-nucleus and bulk rna-seq reveals the molecular mechanism of thalamus haemorrhage-induced central poststroke pain
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10157064/
https://www.ncbi.nlm.nih.gov/pubmed/37153564
http://dx.doi.org/10.3389/fimmu.2023.1174008
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