Increasing evidence indicates heterogeneity in functional and molecular properties of oligodendrocyte lineage cells both during development and under pathologic conditions. In multiple sclerosis, remyelination of grey matter lesions exceeds that in white matter. Here we used cells derived from grey matter versus white matter regions of surgically resected human brain tissue samples, to compare the capacities of human A2B5-positive progenitor cells and mature oligodendrocytes to ensheath synthetic nanofibers, and relate differences to the molecular profiles of these cells. For both cell types, the percentage of ensheathing cells was greater for grey matter versus white matter cells. For both grey matter and white matter samples, the percentage of cells ensheathing nanofibers was greater for A2B5-positive cells versus mature oligodendrocytes. Grey matter A2B5-positive cells were more susceptible than white matter A2B5-positive cells to injury induced by metabolic insults. Bulk RNA sequencing indicated that separation by cell type (A2B5-positive vs mature oligodendrocytes) is more significant than by region but segregation for each cell type by region is apparent. Molecular features of grey matter versus white matter derived A2B5-positive and mature oligodendrocytes were lower expression of mature oligodendrocyte genes and increased expression of early oligodendrocyte lineage genes. Genes and pathways with increased expression in grey matter derived cells with relevance for myelination included those related to responses to external environment, cell-cell communication, cell migration, and cell adhesion. Immune and cell death related genes were up-regulated in grey matter derived cells. We observed a significant number of up-regulated genes shared between the stress/injury and myelination processes, providing a basis for these features. In contrast to oligodendrocyte lineage cells, no functional or molecular heterogeneity was detected in microglia maintained in vitro, likely reflecting the plasticity of these cells ex vivo. The combined functional and molecular data indicate that grey matter human oligodendrocytes have increased intrinsic capacity to myelinate but also increased injury susceptibility, in part reflecting their being at a stage earlier in the oligodendrocyte lineage.

中文翻译：

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灰质与白质人少突胶质细胞的髓鞘形成电位和损伤易感性


越来越多的证据表明，少突胶质细胞系细胞在发育过程中和病理条件下的功能和分子特性存在异质性。在多发性硬化症中，灰质病变的髓鞘再生超过了白质。在这里，我们使用来自手术切除的人脑组织样本的灰质细胞与白质区域的细胞，来比较人 A2B5 阳性祖细胞和成熟少突胶质细胞包裹合成纳米纤维的能力，并将差异与这些细胞的分子谱联系起来。对于这两种细胞类型，灰质细胞的鞘状细胞百分比高于白质细胞。对于灰质和白质样品，A2B5 阳性细胞的包裹纳米纤维的细胞百分比高于成熟的少突胶质细胞。灰质 A2B5 阳性细胞比白质 A2B5 阳性细胞更容易受到代谢损伤诱导的损伤。大量 RNA 测序表明，按细胞类型（A2B5 阳性与成熟少突胶质细胞）的分离比按区域分离更显着，但每种细胞类型的按区域分离是明显的。与白质衍生的 A2B5 阳性和成熟少突胶质细胞相比，灰质的分子特征是成熟少突胶质细胞基因的表达较低，而早期少突胶质细胞谱系基因的表达增加。在与髓鞘形成相关的灰质衍生细胞中表达增加的基因和通路包括与对外部环境的反应、细胞间通讯、细胞迁移和细胞粘附相关的基因和通路。免疫和细胞死亡相关基因在灰质衍生细胞中上调。 我们观察到在应激/损伤和髓鞘形成过程之间共享的大量上调基因，为这些特征提供了基础。与少突胶质细胞谱系细胞相比，在体外维持的小胶质细胞中未检测到功能或分子异质性，这可能反映了这些细胞离体的可塑性。综合功能和分子数据表明，灰质人少突胶质细胞具有增加的髓鞘形成的内在能力，但也增加了损伤敏感性，部分反映了它们处于少突胶质细胞谱系的早期阶段。