Comparative transcriptional analysis of satellite glial cell injury response

Sara Elgaard Jager; Lone Tjener Pallesen; Lin Lin; Francesca Izzi; Alana Miranda Pinheiro; Sara Villa-Hernandez; Paolo Cesare; Christian Bjerggaard Vaegter; Franziska Denk

doi:10.12688/wellcomeopenres.17885.1

Comparative transcriptional analysis of satellite glial cell injury response

Sara Elgaard Jager^*, Lone Tjener Pallesen, Lin Lin, Francesca Izzi, Alana Miranda Pinheiro, Sara Villa-Hernandez, Paolo Cesare, Christian Bjerggaard Vaegter, Franziska Denk

^*Corresponding author for this work

Wolfson SPaRC

Research output: Contribution to journal › Article › peer-review

8 Citations (Scopus)

Abstract

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.

Original language	English
Article number	156
Journal	Wellcome Open Research
Volume	7
DOIs	https://doi.org/10.12688/wellcomeopenres.17885.1
Publication status	Published - 2022

Keywords

Cholesterol biosynthesis
Dorsal root ganglia
Glia cells
Nerve injury
Pain
Satellite glial cells
Single cell RNA sequencing

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10.12688/wellcomeopenres.17885.1

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title = "Comparative transcriptional analysis of satellite glial cell injury response",

abstract = "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.",

keywords = "Cholesterol biosynthesis, Dorsal root ganglia, Glia cells, Nerve injury, Pain, Satellite glial cells, Single cell RNA sequencing",

author = "Jager, {Sara Elgaard} and Pallesen, {Lone Tjener} and Lin Lin and Francesca Izzi and Pinheiro, {Alana Miranda} and Sara Villa-Hernandez and Paolo Cesare and Vaegter, {Christian Bjerggaard} and Franziska Denk",

note = "Publisher Copyright: {\textcopyright} 2022 Jager SE et al.",

year = "2022",

doi = "10.12688/wellcomeopenres.17885.1",

language = "English",

volume = "7",

journal = "Wellcome Open Research",

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T1 - Comparative transcriptional analysis of satellite glial cell injury response

AU - Jager, Sara Elgaard

AU - Pallesen, Lone Tjener

AU - Lin, Lin

AU - Izzi, Francesca

AU - Pinheiro, Alana Miranda

AU - Villa-Hernandez, Sara

AU - Cesare, Paolo

AU - Vaegter, Christian Bjerggaard

AU - Denk, Franziska

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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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JO - Wellcome Open Research

JF - Wellcome Open Research

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ER -

Comparative transcriptional analysis of satellite glial cell injury response

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