Neuroimmunology Unit, Montreal Neurological Institute, McGill University.
Département de Neurosciences, Université de Montréal, Montreal, Quebec, Canada.
J Neuropathol Exp Neurol. 2019 Jun 1;78(6):468-479. doi: 10.1093/jnen/nlz026.
Remyelination in the human CNS is ascribed to progenitor cells rather than previously myelinating oligodendrocytes (OLs). The ganglioside-recognizing antibody A2B5 has been used to isolate putative progenitor cells, whose in vitro features resemble cells labeled as "pre-oligodendrocytes." Here, we compare the transcriptional profiles of adult human brain-derived A2B5 antibody-selected cells (A+) after initial isolation (day in vitro (DIV1)) and after DIV6, with nonselected (A-) cells (mature OLs), with regard to their differentiation state and functional properties. While a number of previously recognized progenitor associated genes, specifically PTPRZ1 and PDGFRα, were upregulated in the A2B5+ population, a number of such genes were comparably expressed in the mature OLs, as were mature myelin genes. Additional progenitor-related genes were upregulated in the A+ population. We show that A2B5+ cells have greater capacity to ensheath nanofibers, a model of myelination potential; consistent with this, ingenuity pathway analysis indicated that A+ cells had upregulated expression of genes within cell growth and cell signaling pathways. Differential expression of cell death/survival pathways complements previous functional studies showing their increased susceptibility to metabolic stress. At DIV6, we observed significantly fewer differentially expressed genes; suggestive of cell maturation occurring in vitro, indicating the complexity in comparing in vitro and in situ cell properties.
人中枢神经系统中的髓鞘再生归因于祖细胞，而不是先前具有髓鞘形成能力的少突胶质细胞 (OLs)。神经节苷脂识别抗体 A2B5 已被用于分离假定的祖细胞，其体外特征类似于被标记为“前少突胶质细胞”的细胞。在这里，我们比较了成人脑源性 A2B5 抗体选择细胞 (A+) 在最初分离 (体外培养第 1 天 (DIV1)) 和 DIV6 后的转录谱，与未选择的 (A-) 细胞 (成熟的 OLs)，与它们的分化状态和功能特性有关。虽然许多先前识别的祖细胞相关基因，特别是 PTPRZ1 和 PDGFRα，在 A2B5+ 群体中上调，但许多这样的基因在成熟 OLs 中表达相似，成熟的髓鞘基因也是如此。A+ 群体中上调了其他与祖细胞相关的基因。我们表明，A2B5+ 细胞具有更大的能力来包裹纳米纤维，这是髓鞘形成潜力的模型；与此一致，通路分析表明 A+ 细胞上调了细胞生长和细胞信号通路中的基因表达。细胞死亡/存活途径的差异表达补充了先前表明其对代谢应激敏感性增加的功能研究。在 DIV6，我们观察到差异表达基因显著减少；提示体外细胞成熟，表明比较体外和原位细胞特性的复杂性。
