德克萨斯大学Lu O. Sun小组在研究中取得进展。他们揭示了髓鞘形成前少突胶质细胞的遗传靶向揭示了活性依赖的髓鞘形成机制。该研究于2025年11月11日发表于国际一流学术期刊《自然—神经科学》杂志上。

在这里，课题组提出了一个CreERT2敲入小鼠系，可以实现遗传标记，谱系追踪，操作和跨中枢神经系统preOL亚群的多模态分析。遗传标记的preOLs是有丝分裂后的，具有独特的形态和独特的转录组学、表观遗传学和电生理特征。preOLs谱系追踪揭示了单母脑少突胶质细胞发生的时空动态。

此外，感觉剥夺下的preOLs命运图谱显示，神经元活动在一个狭窄的成熟窗口内影响preOLs，促进它们的生存和成功整合。总之，他们的工作提供了一种研究preOLs生物学和轴突少突胶质细胞在健康和疾病中的相互作用。

研究人员表示，为了使轴突形成髓鞘，少突胶质前体细胞（OPCs）会停止分裂并分化为髓鞘形成前少突胶质细胞（preOLs），这是髓鞘形成过程中的一个短暂细胞阶段，通常在人类脱髓鞘病变时停止。前轴细胞扩展突起，观察附近的轴突，开始鞘鞘形成。缺乏可视化和操作preOLs的遗传工具阻碍了它们的深入研究。

附：英文原文

Title: Genetic targeting of premyelinating oligodendrocytes reveals activity-dependent myelination mechanisms

Author: Bhambri, Aksheev, Thai, Phu, Wei, Songtao, Bae, Han-Gyu, Reynolds, Payton, Barbosa, Daniela, Sharma, Tripti, Yu, Ze, Xing, Chao, Kim, Jun Hee, Yu, Guoqiang, Sun, Lu O.

Issue&Volume: 2025-11-11

Abstract: To myelinate axons, oligodendrocyte precursor cells (OPCs) must stop dividing and differentiate into premyelinating oligodendrocytes (preOLs), a transient cell stage during myelination that is often stalled at human demyelinating lesions. PreOLs extend processes, surveying nearby axons to begin ensheathment. The lack of genetic tools to visualize and manipulate preOLs has hindered their in-depth study. Here we present a CreERT2 knockin mouse line that enables genetic labeling, lineage tracing, manipulation and multimodal profiling of preOL subsets across the central nervous system. Genetically labeled preOLs are postmitotic, with distinct morphology and unique transcriptomic, epigenetic and electrophysiological features. PreOL lineage tracing revealed spatiotemporal dynamics of oligodendrogenesis across the mouse brain. Moreover, fate mapping of preOLs under sensory deprivation revealed that neuronal activity influences preOLs within a narrow maturation window, promoting their survival and successful integration. Together, our work presents a genetic tool to study preOL biology and axonoligodendrocyte interactions in health and disease.

DOI: 10.1038/s41593-025-02110-1

Source: https://www.nature.com/articles/s41593-025-02110-1