Glial cell crosstalk in the local microenvironment following spinal cord injury
Spinal cord injury (SCI) has a high incidence, significant rates of disability, and substantial economic costs. The response of glial cells is crucial for spinal cord regeneration following SCI. However, the roles of various glial cell types in SCI pathology and their interactions with other cellula...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-09-01
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| Series: | Brain Research Bulletin |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0361923025002485 |
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| author | Erliang Li Yingchao Gao Jianfeng Zhang Peng Zou Huanhuan Qiao Rui Zhang Yansheng Huang |
| author_facet | Erliang Li Yingchao Gao Jianfeng Zhang Peng Zou Huanhuan Qiao Rui Zhang Yansheng Huang |
| author_sort | Erliang Li |
| collection | DOAJ |
| description | Spinal cord injury (SCI) has a high incidence, significant rates of disability, and substantial economic costs. The response of glial cells is crucial for spinal cord regeneration following SCI. However, the roles of various glial cell types in SCI pathology and their interactions with other cellular targets remain poorly understood. Using single-cell RNA sequencing, we characterized the local microenvironment following SCI and isolated three glial cell types—microglia, astrocytes, and oligodendrocytes—at the injury site. Immunofluorescence confirmed the differential expression of these cell types in spinal cord tissues. Four subtypes of microglia were identified: activated, dividing, homeostatic, and inflammatory. Astrocytes were categorized into 11 clusters, while oligodendrocytes were classified into eight clusters. Enrichment analysis indicated that the loss of oligodendrocytes was associated with ferroptosis. The glial cell crosstalk network revealed various interactions, including TIMP1-FGFR2 and PLXNB2-PTN in astrocytes and oligodendrocytes, as well as LGALS3-MERTK, GPR37L1-PSAP, TFRSF1A-GRN, and PGRMC2-CCL4L2 in astrocytes and microglia. A total of 75 drugs were identified through target-drug screening. This study suggests potential differentiation and intricate crosstalk among these three cell types, provides a theoretical framework for simulating the glial cellular microenvironment of SCI, and establishes a foundation for future interventions aimed at targeting various glial cell processes in the treatment of SCI. |
| format | Article |
| id | doaj-art-eabb98cae27b4f61ba4fb5bfa564d36c |
| institution | DOAJ |
| issn | 1873-2747 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Research Bulletin |
| spelling | doaj-art-eabb98cae27b4f61ba4fb5bfa564d36c2025-08-20T03:22:29ZengElsevierBrain Research Bulletin1873-27472025-09-0122911143610.1016/j.brainresbull.2025.111436Glial cell crosstalk in the local microenvironment following spinal cord injuryErliang Li0Yingchao Gao1Jianfeng Zhang2Peng Zou3Huanhuan Qiao4Rui Zhang5Yansheng Huang6Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710000, ChinaDepartment of Orthopaedics, the 942nd Hospital of the Joint Logistics Support Force of the People's Liberation Army of China, Yinchuan, Ningxia 750004, ChinaDepartment of Pharmacy, Eighth Hospital of Xi’an City, Xi’an, Shaanxi, 710000, ChinaDepartment of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710000, ChinaDepartment of Orthopaedics, The Second Affiliated Hospital of Air Force Military Medical University, Xi'an, Shaanxi, 710000, ChinaDepartment of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710000, China; Corresponding authors.Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710000, China; Corresponding authors.Spinal cord injury (SCI) has a high incidence, significant rates of disability, and substantial economic costs. The response of glial cells is crucial for spinal cord regeneration following SCI. However, the roles of various glial cell types in SCI pathology and their interactions with other cellular targets remain poorly understood. Using single-cell RNA sequencing, we characterized the local microenvironment following SCI and isolated three glial cell types—microglia, astrocytes, and oligodendrocytes—at the injury site. Immunofluorescence confirmed the differential expression of these cell types in spinal cord tissues. Four subtypes of microglia were identified: activated, dividing, homeostatic, and inflammatory. Astrocytes were categorized into 11 clusters, while oligodendrocytes were classified into eight clusters. Enrichment analysis indicated that the loss of oligodendrocytes was associated with ferroptosis. The glial cell crosstalk network revealed various interactions, including TIMP1-FGFR2 and PLXNB2-PTN in astrocytes and oligodendrocytes, as well as LGALS3-MERTK, GPR37L1-PSAP, TFRSF1A-GRN, and PGRMC2-CCL4L2 in astrocytes and microglia. A total of 75 drugs were identified through target-drug screening. This study suggests potential differentiation and intricate crosstalk among these three cell types, provides a theoretical framework for simulating the glial cellular microenvironment of SCI, and establishes a foundation for future interventions aimed at targeting various glial cell processes in the treatment of SCI.http://www.sciencedirect.com/science/article/pii/S0361923025002485Single-cell RNA sequencingGlial cellsMicrogliaAstrocytesOligodendrocyte |
| spellingShingle | Erliang Li Yingchao Gao Jianfeng Zhang Peng Zou Huanhuan Qiao Rui Zhang Yansheng Huang Glial cell crosstalk in the local microenvironment following spinal cord injury Brain Research Bulletin Single-cell RNA sequencing Glial cells Microglia Astrocytes Oligodendrocyte |
| title | Glial cell crosstalk in the local microenvironment following spinal cord injury |
| title_full | Glial cell crosstalk in the local microenvironment following spinal cord injury |
| title_fullStr | Glial cell crosstalk in the local microenvironment following spinal cord injury |
| title_full_unstemmed | Glial cell crosstalk in the local microenvironment following spinal cord injury |
| title_short | Glial cell crosstalk in the local microenvironment following spinal cord injury |
| title_sort | glial cell crosstalk in the local microenvironment following spinal cord injury |
| topic | Single-cell RNA sequencing Glial cells Microglia Astrocytes Oligodendrocyte |
| url | http://www.sciencedirect.com/science/article/pii/S0361923025002485 |
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