Discrepancy in the Usage of GFAP as a Marker of Satellite Glial Cell Reactivity

Mohr, Kjeld Morten; Pallesen, Lone Tjener; Richner, Mette; Vægter, Christian Bjerggaard

doi:10.3390/biomedicines9081022

Cited by 21 publications

(27 citation statements)

References 102 publications

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“…Furthermore, we did not observe differential regulation of Gfap above threshold in either dataset ( Table 5 ). Whether this result reflects strain or species variation is discussed elsewhere 47 .…”

Section: Resultsmentioning

confidence: 93%

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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Section: Resultsmentioning

confidence: 93%

Comparative transcriptional analysis of satellite glial cell injury response

et al. 2022

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“…SGC also express glial fibrillary acidic protein (GFAP) and similarly to astrocytes, GFAP expression is increased under pathological conditions, which can have a protective function [82]. In mouse, Gfap is one of the top upregulated genes in SGC upon nerve injury [1; 2; 10; 17], but it is not expressed in all SGC [2; 47]. In uninjured SGC, the distribution of Gfap was relatively low, with ~20% expression in rat, 1.5% in mouse and undetectable levels in human DRG (Fig.…”

Section: Resultsmentioning

confidence: 99%

Profiling the molecular signature of Satellite Glial Cells at the single cell level reveals high similarities between rodent and human

Avraham¹,

Chamessian²,

Feng³

et al. 2021

Preprint

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Peripheral sensory neurons located in dorsal root ganglia relay sensory information from the peripheral tissue to the brain. Satellite glial cells (SGC) are unique glial cells that form an envelope completely surrounding each sensory neuron soma. This organization allows for close bidirectional communication between the neuron and it surrounding glial coat. Morphological and molecular changes in SGC have been observed in multiple pathological conditions such as inflammation, chemotherapy-induced neuropathy, viral infection and nerve injuries. There is evidence that changes in SGC contribute to chronic pain by augmenting neuronal activity in various rodent pain models. SGC also play a critical role in axon regeneration. Whether findings made in rodent model systems are relevant to human physiology have not been investigated. Here we present a detailed characterization of the transcriptional profile of SGC in mouse, rat and human at the single cell level. Our findings suggest that key features of SGC in rodent models are conserved in human. Our study provides the potential to leverage on rodent SGC properties and identify potential targets for the treatment of nerve repair and alleviation of painful conditions.

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“…This increase was statistically significant, but smaller than that observed in a pain model based on lipopolysaccharide injection [ 28 ]. It should be mentioned that TNCB induces local inflammation [ 37 ], and therefore, the GFAP upregulation may not be specific for pruritus, but is a consequence of the inflammation [ 42 ]. For example, local inflammation of the sciatic nerve induced upregulation in GFAP immunostaining in SGCs in dorsal root ganglia [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Satellite Glial Cells and Neurons in Trigeminal Ganglia Are Altered in an Itch Model in Mice

Cohen

Feldman-Goriachnik

Hanani

2022

Cells

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Itch (pruritus) is a common chronic condition with a lifetime prevalence of over 20%. The mechanisms underlying itch are poorly understood, and its therapy is difficult. There is recent evidence that following nerve injury or inflammation, intercellular communications in sensory ganglia are augmented, which may lead to abnormal neuronal activity, and hence to pain, but there is no information whether such changes take place in an itch model. We studied changes in neurons and satellite glial cells (SGCs) in trigeminal ganglia in an itch model in mice using repeated applications of 2,4,6-trinitro-1-chlorobenzene (TNCB) to the external ear over a period of 11 days. Treated mice showed augmented scratching behavior as compared with controls during the application period and for several days afterwards. Immunostaining for the activation marker glial fibrillary acidic protein in SGCs was greater by about 35% after TNCB application, and gap junction-mediated coupling between neurons increased from about 2% to 13%. The injection of gap junction blockers reduced scratching behavior, suggesting that gap junctions contribute to itch. Calcium imaging studies showed increased responses of SGCs to the pain (and presumed itch) mediator ATP. We conclude that changes in both neurons and SGCs in sensory ganglia may play a role in itch.

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Discrepancy in the Usage of GFAP as a Marker of Satellite Glial Cell Reactivity

Cited by 21 publications

References 102 publications

Comparative transcriptional analysis of satellite glial cell injury response

Comparative transcriptional analysis of satellite glial cell injury response

Profiling the molecular signature of Satellite Glial Cells at the single cell level reveals high similarities between rodent and human

Satellite Glial Cells and Neurons in Trigeminal Ganglia Are Altered in an Itch Model in Mice

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