Shengnan Wang1  · Hong Liu1  · Jiali Li1  · Yimin Yuan1,2,3 · Ziwei Dai1  · Zhida Lan1,3 · Chao Huang1,3 · Xiaojie Wei1  · Cheng He1  · Zhida Su1  · Shangyao Qin1

1 Department of Neurobiology, College of Basic Medicine, Key Laboratory of Molecular Neurobiology of the Ministry of Education, Naval Medical University, Shanghai 200433, China 

2 Department of Pain Medicine, School of Anesthesiology, Naval Medical University, Shanghai 200433, China 

3 Department of Anatomy, College of Basic Medicine, Naval Medical University, Shanghai 200433, China

Abstract

Central nervous system (CNS) injuries trigger a complex glial response, in which oligodendrocyte precursor cells (OPCs) play a far more dynamic role than previously recognized. Moving beyond their canonical function as a remyelination reservoir, reactive OPCs emerge as plastic signaling hubs whose fate and function are dictated by injury-specific cues. This review synthesizes recent evidence to propose a novel conceptual framework: the “reactive OPC state code.” We argue that deciphering this code—the molecular signatures that define pro-regenerative, immunomodulatory, or maladaptive OPC states—is the key to understanding functional heterogeneity in CNS injury. We critically analyze how distinct pathological contexts (trauma, ischemia, neuroinflammation) rewrite this code, leading to diverse outcomes. Finally, we pivot from a generic discussion of OPC-directed therapies to advocate for “state-specific targeting” as the next frontier in translational medicine, offering a roadmap for developing precision interventions that steer reactive OPCs towards repair. This perspective aims to redefine OPC reactivity from a passive response to a central, druggable axis in CNS pathology and repair.

Keywords

Central nervous system injury; Oligodendrocyte precursor cells; Cellular reactivity; Remyelination; Cellular plasticity

[SpringerLink]