Gard A L, Pfeiffer S E
Department of Microbiology, University of Connecticut Health Center, Farmington 06032.
Development. 1989 May;106(1):119-32. doi: 10.1242/dev.106.1.119.
Oligodendroglia differentiate asynchronously in the developing central nervous system, passing through a series of stages identified by the sequential expression of specific differentiation antigens, culminating in the formation of the myelin sheath. In the work presented here, oligodendrocyte progenitors at a temporally narrow and well-defined phenotypic stage of development have been isolated in high purity and yield directly from postnatal rat telencephalon. This stage is identified by the expression of the O4 antigen, the earliest recognized surface marker specific for the oligodendroglial lineage, but the absence of the differentiation marker galactosylcerebroside (GalC). These O4+ GalC- progenitors first appear at birth (10(5)/telencephalon), 2-3 days before O4+ GalC+ oligodendrocytes. The work presented here demonstrates that a major subpopulation of O4+ GalC- progenitors (80%), which we have termed 'proligodendrocytes', is fully committed to terminal oligodendrocyte differentiation. A relatively small, maximal set of nutritional supplements are sufficient for proligodendrocytes to carry out the myelinogenic cascade of differentiated gene expression in a temporally normal manner, in quantitatively significant amounts, in normal ratios of myelin protein isoforms, and in a regulated relationship to the inclusion of myelin-specific products into myelin-like membrane sheets. An important corollary is that this step of myelinogenesis does not require contact with other cell types, in particular neurones and astrocytes, nor does it require unknown growth factors unique to these cell types. Additionally under these conditions, there exists a developmentally quiescent subpopulation (20%) of O4+ GalC- cells that may have significance for understanding the progenitors previously described in adult brain and suggested to be instrumental in remyelination under pathological conditions.
少突胶质细胞在发育中的中枢神经系统中异步分化，经历一系列由特定分化抗原的顺序表达所确定的阶段，最终形成髓鞘。在本文所展示的研究中，处于发育过程中一个时间上狭窄且定义明确的表型阶段的少突胶质前体细胞已从新生大鼠端脑中以高纯度和高产量直接分离出来。这个阶段通过O4抗原的表达来确定，O4抗原是最早被识别的少突胶质细胞谱系特异性表面标志物，但不存在分化标志物半乳糖脑苷脂（GalC）。这些O4⁺GalC⁻前体细胞在出生时首次出现（10⁵/端脑），比O4⁺GalC⁺少突胶质细胞早2 - 3天。本文的研究表明，O4⁺GalC⁻前体细胞的一个主要亚群（80%），我们称之为“前少突胶质细胞”，完全致力于终末少突胶质细胞的分化。相对少量且最基本的一组营养补充剂就足以使前少突胶质细胞以时间上正常的方式、在数量上可观地、以髓鞘蛋白异构体的正常比例，并以与将髓鞘特异性产物纳入类髓鞘膜片的调控关系，进行分化基因表达的髓鞘生成级联反应。一个重要的推论是，髓鞘生成的这一步骤不需要与其他细胞类型接触，特别是神经元和星形胶质细胞，也不需要这些细胞类型特有的未知生长因子。此外，在这些条件下，存在一个发育静止的O4⁺GalC⁻细胞亚群（20%），这对于理解先前在成体脑中描述的、并被认为在病理条件下对髓鞘再生起作用的前体细胞可能具有重要意义。
