Related Experiment Video
Updated: Oct 23, 2025
Identifying Microglia and Peripheral Infiltrating Macrophages in the Injured Spinal Cords Using Flow Cytometry
Published on: June 24, 2025
Spinal Cord Injury Induces Permanent Reprogramming of Microglia into a Disease-Associated State Which Contributes to
Ramil Hakim1, Vasilios Zachariadis2, Sreenivasa Raghavan Sankavaram1
1Department of Clinical Neuroscience, Karolinska Institutet, Stockholm S-17177, Sweden.
Abstract:
Microglia are resident myeloid cells of the CNS. Recently, single-cell RNA sequencing (scRNAseq) has enabled description of a disease-associated microglia (DAM) with a role in neurodegeneration and demyelination. In this study, we use scRNAseq to investigate the temporal dynamics of immune cells harvested from the epicenter of traumatic spinal cord injury (SCI) induced in female mice. We find that as a consequence of SCI, baseline microglia undergo permanent transcriptional reprogramming into a previously uncharacterized subtype of microglia with striking similarities to previously reported DAM as well as a distinct microglial state found during development. Using a microglia depletion model we showed that DAM in SCI are derived from baseline microglia and strongly enhance recovery of hindlimb locomotor function following injury.SIGNIFICANCE STATEMENT Although disease-associated microglia (DAM) have been the subject of strong research interest during recent years (Keren-Shaul, 2017; Jordão, 2019), their cellular origin and their role in "normal" acute injury processes is not well understood. Our work directly addresses the origin and the role of DAM in traumatic injury response. Further, we use a microglia depletion model to prove that DAM in spinal cord injury (SCI) are indeed derived from homeostatic microglia, and that they strongly enhance recovery. Thus, in this work we significantly expand the knowledge of immune response to traumatic injury, demonstrate the applicability to human injury via our unique access to injured human spinal cord tissue, and provide the community with a comprehensive dataset for further exploration.
Insights
Disease-associated microglia (DAM) arise from homeostatic microglia after spinal cord injury (SCI) and significantly improve locomotor recovery. These findings reveal DAM
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are the primary immune cells in the central nervous system (CNS).
- Disease-associated microglia (DAM) have been implicated in neurodegenerative diseases.
- The origin and function of DAM in acute injury, like spinal cord injury (SCI), remain unclear.
Purpose of the Study:
- To investigate the temporal dynamics of immune cells following traumatic SCI.
- To characterize the origin and functional role of DAM in the context of SCI.
- To explore the potential of DAM in promoting recovery after SCI.
Main Methods:
- Single-cell RNA sequencing (scRNAseq) was employed to analyze immune cells from the epicenter of SCI in female mice.
- A microglia depletion model was utilized to ascertain the lineage and function of DAM.
- Transcriptional profiling was performed to identify microglial subtypes and their changes post-injury.
Main Results:
- SCI induces permanent transcriptional reprogramming of baseline microglia into a novel subtype resembling DAM and developmental microglia.
- DAM in SCI are derived from homeostatic microglia.
- Depletion of DAM impairs hindlimb locomotor recovery, indicating their crucial role in functional improvement.
Conclusions:
- Homeostatic microglia are reprogrammed into DAM following SCI, contributing to neuroprotection and repair.
- DAM play a critical role in enhancing functional recovery after traumatic spinal cord injury.
- This study provides a comprehensive dataset and insights into immune responses following SCI, with potential implications for human injury.
