Multiple sclerosis (MS) is an inflammatory disease of the central nervous system characterized by myelin loss and progressive neurodegeneration. To understand MS lesion initiation and progression, we generate spatial gene expression maps of white matter (WM) and grey matter (GM) MS lesions. In different MS lesion types, we detect domains characterized by a distinct gene signature, including an identifiable rim around active WM lesions. Expression changes in astrocyte-specific, oligodendrocyte-specific and microglia-specific gene sets characterize the active lesion rims. Furthermore, we identify three WM lesion progression trajectories, predicting how normal-appearing WM can develop into WM active or mixed active–inactive lesions. Our data shed light on the dynamic progression of MS lesions.

多发性硬化症 （MS） 是一种中枢神经系统炎症性疾病，其特征是髓鞘丢失和进行性神经退行性变。为了了解 MS 病变的发生和发展，我们生成了白质 （WM） 和灰质 （GM） MS 病变的空间基因表达图。在不同的 MS 病变类型中，我们检测到以不同基因特征为特征的结构域，包括活动性 WM 病变周围的可识别边缘。星形胶质细胞特异性、少突胶质细胞特异性和小胶质细胞特异性基因集的表达变化表征了活动性病变边缘。此外，我们确定了三种 WM 病变进展轨迹，预测了外观正常的 WM 如何发展成 WM 活动性或混合性活动性-非活动性病变。我们的数据揭示了 MS 病变的动态进展。