Diversity of satellite glia in sympathetic and sensory ganglia

Mapps, Aurelia A; Thomsen, Michael B; Boehm, Erica; Zhao, Haiqing; Hattar, Samer; Kuruvilla, Rejji

doi:10.1101/2021.05.25.445647

Cited by 8 publications

(17 citation statements)

References 82 publications

(113 reference statements)

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“…Macrophages (orange cells) and SGC (green cells) clusters were then specifically plotted for expression of Cd68 and Fabp7, demonstrating that a subset of cells co-express macrophage and SGC markers (Figure 4B). This agrees with other studies reporting that SGC can express immune markers (Donegan et al, 2013;Huang et al, 2021;Jasmin et al, 2010;Mapps et al, 2021;van Velzen et al, 2009;van Weperen et al, 2021). Violin plots for Cd68 and Fabp7 expression across all cell types in the DRG further demonstrate that Cd68 and Fabp7 are highly expressed in cluster 13, which we named the 'Imoonglia' cluster (Figure 4-figure supplement 1A).…”

Section: A Subset Of Macrophages Expressing Glial Markers Is Increased By Injurysupporting

confidence: 92%

“…Interestingly, rat SGC express CD45, but unlike in humans, the CD45 positive cells were only present after nerve injury (Jasmin et al, 2010). Recent scRNAseq studies further support the presence of a populations of SGC enriched in immune-response genes (Mapps et al, 2021;van Weperen et al, 2021). Whether immune cells move to a peri-neuronal position and become Imoonglia or whether SGCs transition from a progenitor state to acquire an immune signature in stressful condition such as after nerve injury remains to be tested.…”

Section: Discussionmentioning

confidence: 99%

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Profiling sensory neuron microenvironment after peripheral and central axon injury reveals key pathways for neural repair

Avraham¹,

Feng²,

Ewan³

et al. 2020

Preprint

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Sensory neurons with cell bodies in dorsal root ganglia (DRG) represent a useful model to study axon regeneration. Whereas regeneration and functional recovery occurs after peripheral nerve injury, spinal cord injury or dorsal root injury is not followed by regenerative outcomes. This results in part from a failure of central injury to elicit a pro-regenerative response in sensory neurons. However, regeneration of sensory axons in peripheral nerves is not entirely cell autonomous. Whether the different regenerative capacities after peripheral or central injury result in part from a lack of response of macrophages, satellite glial cells (SGC) or other non-neuronal cells in the DRG microenvironment remains largely unknown. To answer this question, we performed a single cell transcriptional profiling of DRG in response to peripheral (sciatic nerve crush) and central injuries (dorsal root crush and spinal cord injury). Each cell type responded differently to peripheral and central injuries. Activation of the PPAR signaling pathway in SGC, which promotes axon regeneration after nerve injury, did not occur after central injuries. Treatment with the FDA-approved PPARα agonist fenofibrate, increased axon regeneration after dorsal root injury. This study provides a map of the distinct DRG microenvironment responses to peripheral and central injuries at the single cell level and highlights that manipulating non-neuronal cells could lead to avenues to promote functional recovery after CNS injuries.

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Section: A Subset Of Macrophages Expressing Glial Markers Is Increased By Injurysupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Profiling sensory neuron microenvironment after peripheral and central axon injury reveals key pathways for neural repair

Avraham¹,

Feng²,

Ewan³

et al. 2020

Preprint

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“…It is therefore encouraging that recent advances in single cell RNA sequencing (scRNAseq) have made it possible to study the transcriptional profile of these cells in previously unprecedented detail. To date, six papers and preprints have included such SGC scRNAseq studies in mice, with focus on either development 27 , 28 , species comparison 29 or nerve injury 10 , 30 , 31 . Furthermore, our team published a bulk RNA-seq experiment with focus on nerve injury 13 .…”

Section: Introductionmentioning

confidence: 99%

Comparative transcriptional analysis of satellite glial cell injury response

et al. 2022

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Background: Satellite glial cells (SGCs) tightly surround and support primary sensory neurons in the peripheral nervous system and are increasingly recognized for their involvement in the development of neuropathic pain following nerve injury. SGCs are difficult to investigate due to their flattened shape and tight physical connection to neurons in vivo and their rapid changes in phenotype and protein expression when cultured in vitro. Consequently, several aspects of SGC function under normal conditions as well as after a nerve injury remain to be explored. The recent advance in single cell RNA sequencing (scRNAseq) technologies has enabled a new approach to investigate SGCs. Methods: In this study we used scRNAseq to investigate SGCs from mice subjected to sciatic nerve injury. We used a meta-analysis approach to compare the injury response with that found in other published datasets. Furthermore, we also used scRNAseq to investigate how cells from the dorsal root ganglion (DRG) change after 3 days in culture. Results: From our meta-analysis of the injured conditions, we find that SGCs share a common signature of 18 regulated genes following sciatic nerve crush or sciatic nerve ligation, involving transcriptional regulation of cholesterol biosynthesis. We also observed a considerable transcriptional change when culturing SGCs, suggesting that some differentiate into a specialised in vitro state while others start resembling Schwann cell-like precursors. Conclusion: By using integrated analyses of new and previously published scRNAseq datasets, this study provides a consensus view of which genes are most robustly changed in SGCs after injury. Our results are available via the Broad Institute Single Cell Portal, so that readers can explore and search for genes of interest.

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“…Post-ganglionic neurons, which reside in sympathetic ganglia and project axons to innervate diverse peripheral organs and tissues, mediate key autonomic effects, including cardiac output, metabolism, and immune function ( Goldstein, 2013 ). Satellite glia are the major glial cells in sympathetic ganglia ( Hanani, 2010 ; Mapps et al, 2021 ) and have a unique architecture in completely enveloping neuronal cell bodies ( Elfvin and Forsman, 1978 ; Gabella et al, 1988 ). Each neuron and associated glia are thought to form a discrete structural and functional unit ( Hanani, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

Satellite glia modulate sympathetic neuron survival, activity, and autonomic function

Mapps

Boehm

Beier

et al. 2022

eLife

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Satellite glia are the major glial cells in sympathetic ganglia, enveloping neuronal cell bodies. Despite this intimate association, the extent to which sympathetic functions are influenced by satellite glia in vivo remains unclear. Here, we show that satellite glia are critical for metabolism, survival, and activity of sympathetic neurons and modulate autonomic behaviors in mice. Adult ablation of satellite glia results in impaired mTOR signaling, soma atrophy, reduced noradrenergic enzymes, and loss of sympathetic neurons. However, persisting neurons have elevated activity, and satellite glia-ablated mice show increased pupil dilation and heart rate, indicative of enhanced sympathetic tone. Satellite glia-specific deletion of Kir4.1, an inward-rectifying potassium channel, largely recapitulates the cellular defects observed in glia-ablated mice, suggesting that satellite glia act in part via K+-dependent mechanisms. These findings highlight neuron-satellite glia as functional units in regulating sympathetic output, with implications for disorders linked to sympathetic hyper-activity such as cardiovascular disease and hypertension.

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Diversity of satellite glia in sympathetic and sensory ganglia

Cited by 8 publications

References 82 publications

Profiling sensory neuron microenvironment after peripheral and central axon injury reveals key pathways for neural repair

Profiling sensory neuron microenvironment after peripheral and central axon injury reveals key pathways for neural repair

Comparative transcriptional analysis of satellite glial cell injury response

Satellite glia modulate sympathetic neuron survival, activity, and autonomic function

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