Multi-omics characterization of oncosis in spinal cord injury
Spinal cord injury (SCI) initiates a cascade of complex secondary damage processes, prominently involving programmed cell death (PCD). Although apoptosis and necroptosis have been extensively characterized, the role of oncosis in SCI remains inadequately understood. In this study, we examined the ex...
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Elsevier
2025-08-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996125001986 |
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| author | Zhipeng Jiang Youwei Guo Zihan Wang Jinhao Ouyang Hailong Huang Haoxuan Huang Tianqian Shen Lei Wang Wen Yin Xingjun Jiang Caiping Ren |
| author_facet | Zhipeng Jiang Youwei Guo Zihan Wang Jinhao Ouyang Hailong Huang Haoxuan Huang Tianqian Shen Lei Wang Wen Yin Xingjun Jiang Caiping Ren |
| author_sort | Zhipeng Jiang |
| collection | DOAJ |
| description | Spinal cord injury (SCI) initiates a cascade of complex secondary damage processes, prominently involving programmed cell death (PCD). Although apoptosis and necroptosis have been extensively characterized, the role of oncosis in SCI remains inadequately understood. In this study, we examined the expression dynamics and cellular localization of oncosis-related genes (ORGs) following SCI. We conducted an analysis of bulk RNA-seq data to identify differentially expressed ORGs at five distinct time points post-injury. Six candidate genes (Trp53, Casp3, Jun, Tmem123, Chmp6, Map2) were identified based on their temporal expression patterns. Single-cell RNA sequencing and spatial transcriptomics revealed specific cell-type specificity and lesion-centered spatial enrichment of these genes. Trp53 and Casp3 were found to be rapidly upregulated in neurons and microglia, whereas Tmem123 exhibited a progressive downregulation. Jun emonstrated biphasic activation in astrocytes and oligodendrocytes. In vitro experiments using LPS-treated PC12 cells corroborated key expression trends, with transmission electron microscopy (TEM) confirming the morphological characteristics of oncosis. In vivo, quantitative reverse transcription PCR (qRT-PCR) qRT-PCR and immunofluorescence analyses in a rat SCI model further validated the altered expression of these genes. Significantly, a reduction in Map2 and an elevation in Chmp6 were associated with cytoskeletal collapse and plasma membrane rupture, respectively. Together, our findings provide the first spatiotemporal mapping of oncotic gene regulation following SCI and identify potential targets for therapeutic intervention. |
| format | Article |
| id | doaj-art-2ecce3074fca461bb1765622ce76f9e3 |
| institution | OA Journals |
| issn | 1095-953X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj-art-2ecce3074fca461bb1765622ce76f9e32025-08-20T02:32:05ZengElsevierNeurobiology of Disease1095-953X2025-08-0121210698210.1016/j.nbd.2025.106982Multi-omics characterization of oncosis in spinal cord injuryZhipeng Jiang0Youwei Guo1Zihan Wang2Jinhao Ouyang3Hailong Huang4Haoxuan Huang5Tianqian Shen6Lei Wang7Wen Yin8Xingjun Jiang9Caiping Ren10Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China； Xiangya School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, 410078, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China； Xiangya School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, 410078, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China； Xiangya School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, 410078, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China； Xiangya School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, 410078, China; The NHC Key Laboratory of Carcinogenesis and The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Central South University, Changsha, Hunan Province, 410078, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China； Xiangya School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, 410078, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China； Xiangya School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, 410078, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China； Xiangya School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, 410078, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China； Xiangya School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, 410078, China; The NHC Key Laboratory of Carcinogenesis and The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Central South University, Changsha, Hunan Province, 410078, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China； Xiangya School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, 410078, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Corresponding authors at: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China； Xiangya School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, 410078, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Corresponding authors at: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China； Xiangya School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, 410078, China; The NHC Key Laboratory of Carcinogenesis and The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Central South University, Changsha, Hunan Province, 410078, China; Corresponding authors at: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.Spinal cord injury (SCI) initiates a cascade of complex secondary damage processes, prominently involving programmed cell death (PCD). Although apoptosis and necroptosis have been extensively characterized, the role of oncosis in SCI remains inadequately understood. In this study, we examined the expression dynamics and cellular localization of oncosis-related genes (ORGs) following SCI. We conducted an analysis of bulk RNA-seq data to identify differentially expressed ORGs at five distinct time points post-injury. Six candidate genes (Trp53, Casp3, Jun, Tmem123, Chmp6, Map2) were identified based on their temporal expression patterns. Single-cell RNA sequencing and spatial transcriptomics revealed specific cell-type specificity and lesion-centered spatial enrichment of these genes. Trp53 and Casp3 were found to be rapidly upregulated in neurons and microglia, whereas Tmem123 exhibited a progressive downregulation. Jun emonstrated biphasic activation in astrocytes and oligodendrocytes. In vitro experiments using LPS-treated PC12 cells corroborated key expression trends, with transmission electron microscopy (TEM) confirming the morphological characteristics of oncosis. In vivo, quantitative reverse transcription PCR (qRT-PCR) qRT-PCR and immunofluorescence analyses in a rat SCI model further validated the altered expression of these genes. Significantly, a reduction in Map2 and an elevation in Chmp6 were associated with cytoskeletal collapse and plasma membrane rupture, respectively. Together, our findings provide the first spatiotemporal mapping of oncotic gene regulation following SCI and identify potential targets for therapeutic intervention.http://www.sciencedirect.com/science/article/pii/S0969996125001986Spinal cord injuryOncosisProgrammed cell deathSpatial transcriptomicsSingle-cell RNA-seq |
| spellingShingle | Zhipeng Jiang Youwei Guo Zihan Wang Jinhao Ouyang Hailong Huang Haoxuan Huang Tianqian Shen Lei Wang Wen Yin Xingjun Jiang Caiping Ren Multi-omics characterization of oncosis in spinal cord injury Neurobiology of Disease Spinal cord injury Oncosis Programmed cell death Spatial transcriptomics Single-cell RNA-seq |
| title | Multi-omics characterization of oncosis in spinal cord injury |
| title_full | Multi-omics characterization of oncosis in spinal cord injury |
| title_fullStr | Multi-omics characterization of oncosis in spinal cord injury |
| title_full_unstemmed | Multi-omics characterization of oncosis in spinal cord injury |
| title_short | Multi-omics characterization of oncosis in spinal cord injury |
| title_sort | multi omics characterization of oncosis in spinal cord injury |
| topic | Spinal cord injury Oncosis Programmed cell death Spatial transcriptomics Single-cell RNA-seq |
| url | http://www.sciencedirect.com/science/article/pii/S0969996125001986 |
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