Single-cell analysis reveals temporal heterogeneity of neutrophil-lineage states after spinal cord injury
4 affiliations
- 1Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
- 2Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China; NHC Key Laboratory of Carcinogenesis and The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya School of Basic Medical Sciences, Central South University, Changsha 410008, Hunan Province, China
- 3Bioinformatics Center, College of Biology, Hunan Provincial Key Laboratory of Medical Virology, Hunan University, Changsha 410082, Hunan Province, China
- 4Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China; Corresponding authors at: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.
Abstract
Spinal cord injury (SCI) elicits a complex immune response that evolves from acute inflammation to chronic tissue remodeling, but the temporal organization of neutrophil-lineage cells remains incompletely defined. Here, we reanalyzed three public SCI single-cell RNA sequencing datasets, including immune-cell-enriched and whole-lesion datasets. We combined neutrophil-state annotation, maturation assessment, differential expression, functional module scoring and ligand–receptor inference with immunofluorescence validation in a C57BL/6 mouse contusion model. Neutrophil-lineage cells were detected beyond the acute phase and exhibited temporal variation in the composition of reference-associated G0–G5 states. Cells assigned to G3–G5 displayed predominantly post-mitotic transcriptional profiles and were analyzed together as neutrophils to characterize temporal expression patterns. Inflammatory and chemotactic expression was most prominent early after injury, whereas lipid-associated expression increased at selected later stages alongside persistent inflammatory features. These broad patterns were observed across datasets, with differences in state composition and response timing. Cell–cell communication analysis predicted interactions involving chemokines, thrombospondin and osteopontin between neutrophils and other immune populations. Immunofluorescence showed a higher APOE+ fraction and a lower IL1B+ fraction among Ly6G+ cells at 28 days than at 1 day after injury. These findings reveal sustained, temporally heterogeneous neutrophil-lineage responses and provide a basis for investigating their contributions to inflammation and lesion remodeling after SCI.
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BibTeX
@article{guo2026singlecell,
title = {{Single-cell analysis reveals temporal heterogeneity of neutrophil-lineage states after spinal cord injury}},
author = {Youwei Guo and Lei Wang and Weidong Liu and Ruina You and Zhipeng Jiang and Jinhao Ouyang and Bo Zhou and Xingjun Jiang and Caiping Ren},
journal = {Neurobiology of Disease},
year = {2026},
month = oct,
doi = {10.1016/j.nbd.2026.107660},
url = {https://doi.org/10.1016/j.nbd.2026.107660},
note = {CC BY},
}
RIS
TY - JOUR
TI - Single-cell analysis reveals temporal heterogeneity of neutrophil-lineage states after spinal cord injury
AU - Youwei Guo
AU - Lei Wang
AU - Weidong Liu
AU - Ruina You
AU - Zhipeng Jiang
AU - Jinhao Ouyang
AU - Bo Zhou
AU - Xingjun Jiang
AU - Caiping Ren
PY - 2026
DA - 2026/10/30
JO - Neurobiology of Disease
DO - 10.1016/j.nbd.2026.107660
UR - https://doi.org/10.1016/j.nbd.2026.107660
AB - Spinal cord injury (SCI) elicits a complex immune response that evolves from acute inflammation to chronic tissue remodeling, but the temporal organization of neutrophil-lineage cells remains incompletely defined. Here, we reanalyzed three public SCI single-cell RNA sequencing datasets, including immune-cell-enriched and whole-lesion datasets. We combined neutrophil-state annotation, maturation assessment, differential expression, functional module scoring and ligand–receptor inference with immunofluorescence validation in a C57BL/6 mouse contusion model. Neutrophil-lineage cells were detected beyond the acute phase and exhibited temporal variation in the composition of reference-associated G0–G5 states. Cells assigned to G3–G5 displayed predominantly post-mitotic transcriptional profiles and were analyzed together as neutrophils to characterize temporal expression patterns. Inflammatory and chemotactic expression was most prominent early after injury, whereas lipid-associated expression increased at selected later stages alongside persistent inflammatory features. These broad patterns were observed across datasets, with differences in state composition and response timing. Cell–cell communication analysis predicted interactions involving chemokines, thrombospondin and osteopontin between neutrophils and other immune populations. Immunofluorescence showed a higher APOE+ fraction and a lower IL1B+ fraction among Ly6G+ cells at 28 days than at 1 day after injury. These findings reveal sustained, temporally heterogeneous neutrophil-lineage responses and provide a basis for investigating their contributions to inflammation and lesion remodeling after SCI.
SN - 1095-953X
SN - 0969-9961
ER -