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Multi-omics identifies a VIM-associated microglial program linked to lactylation, ferroptosis, and neuroinflammation after spinal cord injury

Year: 2026

Type: article

Abstract: Background: The secondary injury cascade following spinal cord injury (SCI) involves substantial metabolic reprogramming and immune responses. However, whether transcriptional signatures related to lactylation, ferroptosis, and neuroinflammation show coordinated changes after SCI, and which cellular states are associated with these signatures, remain unclear. Methods: perturbation analysis. A C5 unilateral contusion SCI mouse model was used for transcriptomic validation, behavioral assessments, Western blotting, and immunofluorescence. Human peripheral blood RNA-seq data (GSE151371) were used as an exploratory external reference for systemic SCI-associated expression patterns. Results: Bulk transcriptomic analysis revealed coordinated elevation of lactylation-related, ferroptosis-related, and inflammation-related signature scores after SCI, with the highest scores observed at 3 days post-injury. Single-cell RNA-seq localized these signatures predominantly to expanded disease-associated microglia (DAM)-like states. Network screening prioritized vimentin (Vim) as a candidate hub gene associated with the three signatures, and Vim-high pathological microglia exhibited an activated inflammatory-metabolic transcriptional state. In the SCI mouse model, VIM, pan-lysine lactylation (pan-Kla), acyl-CoA synthetase long-chain family member 4 (ACSL4), and interleukin-1β (IL-1β) were upregulated in whole-lesion spinal cord tissue. Immunofluorescence further showed increased VIM, pan-Kla, and ACSL4 signals with spatial overlap within IBA1-positive cells after SCI. Conclusion: Pathological DAM-like microglia represent major microglial states exhibiting concurrent lactylation-related, ferroptosis-related, and inflammatory signatures after SCI. VIM was prioritized as a candidate hub associated with this pathological microglial program. These findings provide a cellular and molecular framework for future mechanistic studies of secondary SCI.

Source: Frontiers in Genetics

DOI: 10.3389/fgene.2026.1902559

Authors: Jiayu Chen, Kai Chen, Zucheng Huang, Jie Tong

Institutions: Chenzhou First People's Hospital, Wenzhou Medical University, Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Nanfang Hospital, Southern Medical University

Language: English

Topic: Spinal Cord Injury Research

Subfield: Pathology and Forensic Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801