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Muscle denervation promotes functional interactions between glial and mesenchymal cells through NGFR and NGF

We performed scRNA-seq/snATAC-seq of skeletal muscles post sciatic nerve transection to delineate cell type-specific patterns of gene expression/chromatin accessibility at different time points post-denervation. Unlike myotrauma, denervation selectively activates glial cells and Thy1/CD90-expressing...

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Autores principales: Nicoletti, Chiara, Wei, Xiuqing, Etxaniz, Usue, D’Ercole, Chiara, Madaro, Luca, Perera, Ranjan, Puri, Pier Lorenzo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10319848/
https://www.ncbi.nlm.nih.gov/pubmed/37416457
http://dx.doi.org/10.1016/j.isci.2023.107114
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author Nicoletti, Chiara
Wei, Xiuqing
Etxaniz, Usue
D’Ercole, Chiara
Madaro, Luca
Perera, Ranjan
Puri, Pier Lorenzo
author_facet Nicoletti, Chiara
Wei, Xiuqing
Etxaniz, Usue
D’Ercole, Chiara
Madaro, Luca
Perera, Ranjan
Puri, Pier Lorenzo
author_sort Nicoletti, Chiara
collection PubMed
description We performed scRNA-seq/snATAC-seq of skeletal muscles post sciatic nerve transection to delineate cell type-specific patterns of gene expression/chromatin accessibility at different time points post-denervation. Unlike myotrauma, denervation selectively activates glial cells and Thy1/CD90-expressing mesenchymal cells. Glial cells expressed Ngf receptor (Ngfr) and were located near neuromuscular junctions (NMJs), close to Thy1/CD90-expressing cells, which provided the main cellular source of NGF post-denervation. Functional communication between these cells was mediated by NGF/NGFR, as either recombinant NGF or co-culture with Thy1/CD90-expressing cells could increase glial cell number ex vivo. Pseudo-time analysis in glial cells revealed an initial bifurcation into processes related to either cellular de-differentiation/commitment to specialized cell types (e.g., Schwann cells), or failure to promote nerve regeneration, leading to extracellular matrix remodeling toward fibrosis. Thus, interactions between denervation-activated Thy1/CD90-expressing and glial cells represent an early abortive process toward NMJs repair, ensued by the conversion of denervated muscles into an environment hostile for NMJ repair.
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spelling pubmed-103198482023-07-06 Muscle denervation promotes functional interactions between glial and mesenchymal cells through NGFR and NGF Nicoletti, Chiara Wei, Xiuqing Etxaniz, Usue D’Ercole, Chiara Madaro, Luca Perera, Ranjan Puri, Pier Lorenzo iScience Article We performed scRNA-seq/snATAC-seq of skeletal muscles post sciatic nerve transection to delineate cell type-specific patterns of gene expression/chromatin accessibility at different time points post-denervation. Unlike myotrauma, denervation selectively activates glial cells and Thy1/CD90-expressing mesenchymal cells. Glial cells expressed Ngf receptor (Ngfr) and were located near neuromuscular junctions (NMJs), close to Thy1/CD90-expressing cells, which provided the main cellular source of NGF post-denervation. Functional communication between these cells was mediated by NGF/NGFR, as either recombinant NGF or co-culture with Thy1/CD90-expressing cells could increase glial cell number ex vivo. Pseudo-time analysis in glial cells revealed an initial bifurcation into processes related to either cellular de-differentiation/commitment to specialized cell types (e.g., Schwann cells), or failure to promote nerve regeneration, leading to extracellular matrix remodeling toward fibrosis. Thus, interactions between denervation-activated Thy1/CD90-expressing and glial cells represent an early abortive process toward NMJs repair, ensued by the conversion of denervated muscles into an environment hostile for NMJ repair. Elsevier 2023-06-13 /pmc/articles/PMC10319848/ /pubmed/37416457 http://dx.doi.org/10.1016/j.isci.2023.107114 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Nicoletti, Chiara
Wei, Xiuqing
Etxaniz, Usue
D’Ercole, Chiara
Madaro, Luca
Perera, Ranjan
Puri, Pier Lorenzo
Muscle denervation promotes functional interactions between glial and mesenchymal cells through NGFR and NGF
title Muscle denervation promotes functional interactions between glial and mesenchymal cells through NGFR and NGF
title_full Muscle denervation promotes functional interactions between glial and mesenchymal cells through NGFR and NGF
title_fullStr Muscle denervation promotes functional interactions between glial and mesenchymal cells through NGFR and NGF
title_full_unstemmed Muscle denervation promotes functional interactions between glial and mesenchymal cells through NGFR and NGF
title_short Muscle denervation promotes functional interactions between glial and mesenchymal cells through NGFR and NGF
title_sort muscle denervation promotes functional interactions between glial and mesenchymal cells through ngfr and ngf
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10319848/
https://www.ncbi.nlm.nih.gov/pubmed/37416457
http://dx.doi.org/10.1016/j.isci.2023.107114
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