Imaging resident and recruited macrophage contribution to Wallerian degeneration

Boissonnas, Alexandre; Louboutin, Floriane; Laviron, Marie; Loyher, Pierre-Louis; Reboussin, Élodie; Barthélémy, Sandrine; Goazigo, Annabelle Réaux‐Le; Lobsiger, Christian S.; Combadière, Béhazine; Parsadaniantz, Stéphane Melik; Combadière, Christophe

doi:10.1084/jem.20200471

Cited by 28 publications

(19 citation statements)

References 39 publications

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“…Gene expression changes following peripheral nerve injury have been extensively studied by microarray analysis and bulk mRNA sequencing (Arthur-Farraj et al, 2012 , 2017 ; Fontana et al, 2012 ; Jessen and Mirsky, 2016 ; Clements et al, 2017 ; Gokbuget et al, 2018 ; Norrmen et al, 2018 ; Stratton et al, 2018 ; Tomlinson et al, 2018 ; Boissonnas et al, 2020 ; Ydens et al, 2020 ). However, cell type specific gene expression changes have not been studied.…”

Section: Resultsmentioning

confidence: 99%

“…Currently, there are no clear markers to distinguish activated resident macrophages from infiltrated macrophages in injured nerves (Amann and Prinz, 2020 ; Kolter et al, 2020 ). A recent publication using both Csf1r-ECFP and Cx3cr1-EGFP mice demonstrated that resident macrophages have distinct function and morphological difference from recruited macrophages (Boissonnas et al, 2020 ). Macrophages in the distal nerve could be identified with macrophage marker genes Aif1/Iba1, Cd68, and Mrc1/Cd206.…”

Section: Discussionmentioning

confidence: 99%

“…(D) Split view of cell clusters at resolution 1.9 for intact sciatic nerve and sciatic nerves at day 3 and day 9 post-injury. Jessen and Mirsky, 2016;Clements et al, 2017;Gokbuget et al, 2018;Norrmen et al, 2018;Stratton et al, 2018;Tomlinson et al, 2018;Boissonnas et al, 2020;Ydens et al, 2020). However, cell type specific gene expression changes have not been studied.…”

Section: Changes In the Molecular Profile Of Each Cell Type Followingmentioning

confidence: 99%

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Single Cell Transcriptome Data Analysis Defines the Heterogeneity of Peripheral Nerve Cells in Homeostasis and Regeneration

Chen

Banton

Singh

et al. 2021

Front. Cell. Neurosci.

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The advances in single-cell RNA sequencing technologies and the development of bioinformatics pipelines enable us to more accurately define the heterogeneity of cell types in a selected tissue. In this report, we re-analyzed recently published single-cell RNA sequencing data sets and provide a rationale to redefine the heterogeneity of cells in both intact and injured mouse peripheral nerves. Our analysis showed that, in both intact and injured peripheral nerves, cells could be functionally classified into four categories: Schwann cells, nerve fibroblasts, immune cells, and cells associated with blood vessels. Nerve fibroblasts could be sub-clustered into epineurial, perineurial, and endoneurial fibroblasts. Identified immune cell clusters include macrophages, mast cells, natural killer cells, T and B lymphocytes as well as an unreported cluster of neutrophils. Cells associated with blood vessels include endothelial cells, vascular smooth muscle cells, and pericytes. We show that endothelial cells in the intact mouse sciatic nerve have three sub-types: epineurial, endoneurial, and lymphatic endothelial cells. Analysis of cell type-specific gene changes revealed that Schwann cells and endoneurial fibroblasts are the two most important cell types promoting peripheral nerve regeneration. Analysis of communication between these cells identified potential signals for early blood vessel regeneration, neutrophil recruitment of macrophages, and macrophages activating Schwann cells. Through this analysis, we also report appropriate marker genes for future single cell transcriptome data analysis to identify cell types in intact and injured peripheral nerves. The findings from our analysis could facilitate a better understanding of cell biology of peripheral nerves in homeostasis, regeneration, and disease.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Changes In the Molecular Profile Of Each Cell Type Followingmentioning

confidence: 99%

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Single Cell Transcriptome Data Analysis Defines the Heterogeneity of Peripheral Nerve Cells in Homeostasis and Regeneration

Chen

Banton

Singh

et al. 2021

Front. Cell. Neurosci.

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“…The latent phase lasts up to 36 h wherein the axons appear normal and for much of this time retain the ability to conduct an action potential, although the axon becomes committed to degenerate ( Tsao et al, 1999 ; Beirowski et al, 2004 ; Beirowski et al, 2005 ; Conforti et al, 2014 ). This is also the stage in which the immune system is first seen to be involved; tissue-resident macrophages are activated and bone-marrow derived macrophages, neutrophils and phagocytes infiltrate into the nerve ( Perkins and Tracey, 2000 ; Sta et al, 2014 ; Zigmond and Echevarria, 2019 ; Boissonnas et al, 2020 ; Ydens et al, 2020 ; Chen et al, 2021 ). There is also an injury-associated increase in the levels of cytokines ( Yi et al, 2017 ).…”

Section: Axon Degeneration Research From 1850 To Todaymentioning

confidence: 99%

“…The axons fragment and the compound action potential is lost as they become non-functional ( Beirowski et al, 2004 ; Beirowski et al, 2005 ; Conforti et al, 2014 ; Sta et al, 2014 ). Neutrophils may contribute in the early stages of the execution of degeneration by phagocytosing axonal debris ( Lindborg et al, 2017 ), whilst macrophages clear myelin and axonal debris and later are involved in the axon regeneration process ( Boissonnas et al, 2020 ).…”

Section: Axon Degeneration Research From 1850 To Todaymentioning

confidence: 99%

A Novel NAD Signaling Mechanism in Axon Degeneration and its Relationship to Innate Immunity

Hopkins

Kobe

et al. 2021

Front. Mol. Biosci.

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Axon degeneration represents a pathological feature of many neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease where axons die before the neuronal soma, and axonopathies, such as Charcot-Marie-Tooth disease and hereditary spastic paraplegia. Over the last two decades, it has slowly emerged that a central signaling pathway forms the basis of this process in many circumstances. This is an axonal NAD-related signaling mechanism mainly regulated by the two key proteins with opposing roles: the NAD-synthesizing enzyme NMNAT2, and SARM1, a protein with NADase and related activities. The crosstalk between the axon survival factor NMNAT2 and pro-degenerative factor SARM1 has been extensively characterized and plays an essential role in maintaining the axon integrity. This pathway can be activated in necroptosis and in genetic, toxic or metabolic disorders, physical injury and neuroinflammation, all leading to axon pathology. SARM1 is also known to be involved in regulating innate immunity, potentially linking axon degeneration to the response to pathogens and intercellular signaling. Understanding this NAD-related signaling mechanism enhances our understanding of the process of axon degeneration and enables a path to the development of drugs for a wide range of neurodegenerative diseases.

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Remodeling of the Intra‐Conduit Inflammatory Microenvironment to Improve Peripheral Nerve Regeneration with a Neuromechanical Matching Protein‐Based Conduit

Wang,

Yuan,

Zhang

et al. 2024

Advanced Science

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Peripheral nerve injury (PNI) remains a challenging area in regenerative medicine. Nerve guide conduit (NGC) transplantation is a common treatment for PNI, but the prognosis of NGC treatment is unsatisfactory due to 1) neuromechanical unmatching and 2) the intra‐conduit inflammatory microenvironment (IME) resulting from Schwann cell pyroptosis and inflammatory‐polarized macrophages. A neuromechanically matched NGC composed of regenerated silk fibroin (RSF) loaded with poly(3,4‐ethylenedioxythiophene): poly(styrene sulfonate) (P:P) and dimethyl fumarate (DMF) are designed, which exhibits a matched elastic modulus (25.1 ± 3.5 MPa) for the peripheral nerve and the highest 80% elongation at break, better than most protein‐based conduits. Moreover, the NGC can gradually regulate the intra‐conduit IME by releasing DMF and monitoring sciatic nerve movements via piezoresistive sensing. The combination of NGC and electrical stimulation modulates the IME to support PNI regeneration by synergistically inhibiting Schwann cell pyroptosis and reducing inflammatory factor release, shifting macrophage polarization from the inflammatory M1 phenotype to the tissue regenerative M2 phenotype and resulting in functional recovery of neurons. In a rat sciatic nerve crush model, NGC promoted remyelination and functional and structural regeneration. Generally, the DMF/RSF/P:P conduit provides a new potential therapeutic approach to promote nerve repair in future clinical treatments.

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Imaging resident and recruited macrophage contribution to Wallerian degeneration

Cited by 28 publications

References 39 publications

Single Cell Transcriptome Data Analysis Defines the Heterogeneity of Peripheral Nerve Cells in Homeostasis and Regeneration

Single Cell Transcriptome Data Analysis Defines the Heterogeneity of Peripheral Nerve Cells in Homeostasis and Regeneration

A Novel NAD Signaling Mechanism in Axon Degeneration and its Relationship to Innate Immunity

Remodeling of the Intra‐Conduit Inflammatory Microenvironment to Improve Peripheral Nerve Regeneration with a Neuromechanical Matching Protein‐Based Conduit

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