Noble Mark, Pröschel Chris, Mayer-Pröschel Margot
Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY 14642, USA.
Dev Biol. 2004 Jan 1;265(1):33-52. doi: 10.1016/j.ydbio.2003.06.002.
One of the most extensively studied of mammalian cells is the oligodendrocyte, the myelin-forming cell of the central nervous system. The ancestry and development of this cell have been studied with every approach utilized by developmental biologists. Such detailed efforts have the potential of providing paradigms of relevance to those interested in analyzing the ancestry and development of any cell type. One of the striking features of studies on the development of oligodendrocytes is that different analytical approaches have led to strikingly different theoretical views regarding the ancestry of these cells. On one extreme is the hypothesis that the steps leading to the generation of oligodendrocytes begin with the generation of a glial-restricted precursor (GRP) cell from neuroepithelial stem cells. GRP cells are thought to be capable of giving rise to all glial cells (including oligodendrocytes and multiple astrocyte populations), but not to neurons, a process that appears to require progression through further stages of greater lineage restriction. On the other extreme is the hypothesis that oligodendrocytes are derived from a precursor cell that generates only motor neurons and oligodendrocytes, with astrocytes being generated through a separate lineage. In this review, we critically consider the various contributions to understanding the ancestry of oligodendrocytes, with particular attention to the respective merits of the GRP cell vs. the motor neuron-oligodendrocyte precursor (MNOP) cell hypothesis. We draw the conclusion that, at present, the strengths of the GRP cell hypothesis outweigh those of the MNOP hypothesis and other hypotheses suggesting oligodendrocytes are developmentally more related to motor neurons than to astrocytes. Moreover, it is clear from existing data that, following the period of motor neuron generation, the major glial precursor cell in the embryonic spinal cord is the GRP cell, and that multiple previous studies on the earliest stages of oligodendrocyte generation in the developing spinal cord have been focused on a differentiation stage of GRP cells.
少突胶质细胞是哺乳动物细胞中研究最为广泛的细胞之一,它是中枢神经系统中形成髓鞘的细胞。发育生物学家运用各种方法研究了这种细胞的起源和发育。这些细致的研究有可能为那些想要分析任何细胞类型的起源和发育的人提供相关范例。少突胶质细胞发育研究的一个显著特点是,不同的分析方法导致了关于这些细胞起源的截然不同的理论观点。一种极端的假说是,导致少突胶质细胞产生的步骤始于神经上皮干细胞产生神经胶质限制前体细胞(GRP)。GRP细胞被认为能够产生所有的胶质细胞(包括少突胶质细胞和多种星形胶质细胞群体),但不能产生神经元,这一过程似乎需要经过进一步的、谱系限制更强的阶段。另一种极端的假说是,少突胶质细胞来源于一种仅产生运动神经元和少突胶质细胞的前体细胞,而星形胶质细胞则通过单独的谱系产生。在这篇综述中,我们批判性地思考了在理解少突胶质细胞起源方面的各种贡献,特别关注了GRP细胞与运动神经元 - 少突胶质细胞前体细胞(MNOP)假说各自的优点。我们得出的结论是,目前,GRP细胞假说的优势超过了MNOP假说以及其他认为少突胶质细胞在发育上与运动神经元的关系比与星形胶质细胞的关系更密切的假说。此外,从现有数据可以清楚地看出,在运动神经元产生阶段之后,胚胎脊髓中的主要胶质前体细胞是GRP细胞,并且之前关于发育中的脊髓少突胶质细胞产生最早阶段的多项研究都集中在GRP细胞的分化阶段。