Single-cell transcriptome analysis reveals the immune heterogeneity and the repopulation of microglia by Hif1α in mice after spinal cord injury
Abstract Neuroinflammation is regarded as a vital pathological process in spinal cord injury (SCI), which removes damaged tissue, secretes cytokines, and facilitates regeneration. Repopulation of microglia has been shown to favor recovery from SCI. However, the origin and regulatory factors of micro...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2022-05-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-022-04864-z |
| _version_ | 1818200886723215360 |
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| author | Jingyu Wang Lintao Xu Weiwei Lin Yin Yao Heyangzi Li Gerong Shen Xi Cao Ning He Jun Chen Jue Hu Mingzhi Zheng Xinghui Song Yuemin Ding Yueliang Shen Jinjie Zhong Lin-lin Wang Ying-ying Chen Yongjian Zhu |
| author_facet | Jingyu Wang Lintao Xu Weiwei Lin Yin Yao Heyangzi Li Gerong Shen Xi Cao Ning He Jun Chen Jue Hu Mingzhi Zheng Xinghui Song Yuemin Ding Yueliang Shen Jinjie Zhong Lin-lin Wang Ying-ying Chen Yongjian Zhu |
| author_sort | Jingyu Wang |
| collection | DOAJ |
| description | Abstract Neuroinflammation is regarded as a vital pathological process in spinal cord injury (SCI), which removes damaged tissue, secretes cytokines, and facilitates regeneration. Repopulation of microglia has been shown to favor recovery from SCI. However, the origin and regulatory factors of microglia repopulation after SCI remain unknown. Here, we used single-cell RNA sequencing to portray the dynamic transcriptional landscape of immune cells during the early and late phases of SCI in mice. B cells and migDCs, located in the meninges under physiological conditions, are involved in immune surveillance. Microglia quickly reduced, and peripheral myeloid cells infiltrated three days-post-injury (dpi). At 14 dpi, microglia repopulated, myeloid cells were reduced, and lymphocytes infiltrated. Importantly, genetic lineage tracing of nestin+ and Cx3cr1+ cells in vivo showed that the repopulation of microglia was derived from residual microglia after SCI. We found that residual microglia regress to a developmental growth state in the early stages after SCI. Hif1α promotes microglial proliferation. Conditional ablation of Hif1α in microglia causes larger lesion sizes, fewer axon fibers, and impaired functional recovery in the late stages after SCI. Our results mapped the immune heterogeneity in SCI and raised the possibility that targeting Hif1α may help in axon regeneration and functional recovery after SCI. |
| first_indexed | 2024-12-12T02:44:47Z |
| format | Article |
| id | doaj.art-cdba24521332401790525fc5eddd4fc4 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-12-12T02:44:47Z |
| publishDate | 2022-05-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-cdba24521332401790525fc5eddd4fc42022-12-22T00:41:04ZengNature Publishing GroupCell Death and Disease2041-48892022-05-0113511210.1038/s41419-022-04864-zSingle-cell transcriptome analysis reveals the immune heterogeneity and the repopulation of microglia by Hif1α in mice after spinal cord injuryJingyu Wang0Lintao Xu1Weiwei Lin2Yin Yao3Heyangzi Li4Gerong Shen5Xi Cao6Ning He7Jun Chen8Jue Hu9Mingzhi Zheng10Xinghui Song11Yuemin Ding12Yueliang Shen13Jinjie Zhong14Lin-lin Wang15Ying-ying Chen16Yongjian Zhu17Department of Neurosurgery, Second Affiliated Hospital of Zhejiang University School of Medicine, Key Laboratory of Precise Treatment and Clinical Translational Research of Neurological DiseasesDepartment of Neurosurgery, Second Affiliated Hospital of Zhejiang University School of Medicine, Key Laboratory of Precise Treatment and Clinical Translational Research of Neurological DiseasesDepartment of Neurosurgery, Second Affiliated Hospital of Zhejiang University School of Medicine, Key Laboratory of Precise Treatment and Clinical Translational Research of Neurological DiseasesDepartment of Neurointensive Care Unit, Second Affiliated Hospital of Zhejiang University School of MedicineDepartment of Basic Medicine Sciences, Zhejiang University School of MedicineDepartment of Basic Medicine Sciences, Zhejiang University School of MedicineDepartment of Basic Medicine Sciences, Zhejiang University School of MedicineDepartment of Basic Medicine Sciences, Zhejiang University School of MedicineDepartment of Basic Medicine Sciences, Zhejiang University School of MedicineSchool of Basic Medical Sciences & Forensic Medicine of Hangzhou Medical CollegeSchool of Basic Medical Sciences & Forensic Medicine of Hangzhou Medical CollegeCore Facilities, Zhejiang University School of MedicineSchool of Medicine, Zhejiang University City CollegeDepartment of Basic Medicine Sciences, Zhejiang University School of MedicineDepartment of Basic Medicine Sciences, and Department of Obstetrics of the Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Basic Medicine Sciences, and Department of Orthopaedics of Sir Run Run Shaw Hospital, Zhejiang University School of MedicineDepartment of Basic Medicine Sciences, and Department of Obstetrics of the Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Neurosurgery, Second Affiliated Hospital of Zhejiang University School of Medicine, Key Laboratory of Precise Treatment and Clinical Translational Research of Neurological DiseasesAbstract Neuroinflammation is regarded as a vital pathological process in spinal cord injury (SCI), which removes damaged tissue, secretes cytokines, and facilitates regeneration. Repopulation of microglia has been shown to favor recovery from SCI. However, the origin and regulatory factors of microglia repopulation after SCI remain unknown. Here, we used single-cell RNA sequencing to portray the dynamic transcriptional landscape of immune cells during the early and late phases of SCI in mice. B cells and migDCs, located in the meninges under physiological conditions, are involved in immune surveillance. Microglia quickly reduced, and peripheral myeloid cells infiltrated three days-post-injury (dpi). At 14 dpi, microglia repopulated, myeloid cells were reduced, and lymphocytes infiltrated. Importantly, genetic lineage tracing of nestin+ and Cx3cr1+ cells in vivo showed that the repopulation of microglia was derived from residual microglia after SCI. We found that residual microglia regress to a developmental growth state in the early stages after SCI. Hif1α promotes microglial proliferation. Conditional ablation of Hif1α in microglia causes larger lesion sizes, fewer axon fibers, and impaired functional recovery in the late stages after SCI. Our results mapped the immune heterogeneity in SCI and raised the possibility that targeting Hif1α may help in axon regeneration and functional recovery after SCI.https://doi.org/10.1038/s41419-022-04864-z |
| spellingShingle | Jingyu Wang Lintao Xu Weiwei Lin Yin Yao Heyangzi Li Gerong Shen Xi Cao Ning He Jun Chen Jue Hu Mingzhi Zheng Xinghui Song Yuemin Ding Yueliang Shen Jinjie Zhong Lin-lin Wang Ying-ying Chen Yongjian Zhu Single-cell transcriptome analysis reveals the immune heterogeneity and the repopulation of microglia by Hif1α in mice after spinal cord injury Cell Death and Disease |
| title | Single-cell transcriptome analysis reveals the immune heterogeneity and the repopulation of microglia by Hif1α in mice after spinal cord injury |
| title_full | Single-cell transcriptome analysis reveals the immune heterogeneity and the repopulation of microglia by Hif1α in mice after spinal cord injury |
| title_fullStr | Single-cell transcriptome analysis reveals the immune heterogeneity and the repopulation of microglia by Hif1α in mice after spinal cord injury |
| title_full_unstemmed | Single-cell transcriptome analysis reveals the immune heterogeneity and the repopulation of microglia by Hif1α in mice after spinal cord injury |
| title_short | Single-cell transcriptome analysis reveals the immune heterogeneity and the repopulation of microglia by Hif1α in mice after spinal cord injury |
| title_sort | single cell transcriptome analysis reveals the immune heterogeneity and the repopulation of microglia by hif1α in mice after spinal cord injury |
| url | https://doi.org/10.1038/s41419-022-04864-z |
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