Macroglia, comprising astrocytes and oligodendroglial lineage cells, have long been regarded as uniform cell types of the central nervous system (CNS). Although regional morphological differences between these cell types were initially described after their identification a century ago, these differences were largely ignored. Recently, accumulating evidence suggests that macroglial cells form distinct populations throughout the CNS, based on both functional and morphological features. Moreover, with the use of refined techniques including single-cell and single-nucleus RNA sequencing, additional evidence is emerging for regional macroglial heterogeneity at the transcriptional level. In parallel, several studies revealed the existence of regional differences in remyelination capacity between CNS grey and white matter areas, both in experimental models for successful remyelination as well as in the chronic demyelinating disease multiple sclerosis (MS). In this review, we provide an overview of the diversity in oligodendroglial lineage cells and astrocytes from the grey and white matter, as well as their interplay in health and upon demyelination and successful remyelination. In addition, we discuss the implications of regional macroglial diversity for remyelination in light of its failure in MS. Since the etiology of MS remains unknown and only disease-modifying treatments altering the immune response are available for MS, the elucidation of macroglial diversity in grey and white matter and its putative contribution to the observed difference in remyelination efficiency between these regions may open therapeutic avenues aimed at enhancing endogenous remyelination in either area.

长期以来，包括星形胶质细胞和少突胶质细胞系的巨胶质细胞一直被认为是中枢神经系统（CNS）的统一细胞类型。虽然这些细胞类型之间的区域形态差异最初是在一个世纪前鉴定出来的，但这些差异在很大程度上被忽略了。最近，越来越多的证据表明，基于功能和形态学特征，大胶质细胞在整个CNS中形成不同的种群。此外，通过使用包括单细胞和单核RNA测序在内的完善技术，在转录水平上有关区域大胶质细胞异质性的新证据正在涌现。同时，多项研究表明，中枢神经系统灰质和白质区域之间的髓鞘再生能力存在区域差异，在成功实现髓鞘再生的实验模型以及慢性脱髓鞘疾病多发性硬化症（MS）中均是如此。在这篇综述中，我们概述了来自灰质和白质的少突神经胶质谱系细胞和星形胶质细胞的多样性，以及它们在健康以及脱髓鞘和成功的髓鞘再生中的相互作用。此外，鉴于其在MS中的失败，我们讨论了区域大胶质细胞多样性对髓鞘再生的影响。由于MS的病因仍然未知，并且只有可改变免疫应答的疾病改良疗法可用于MS，