Heterogeneity of NG2 Glial Cells

描述（由申请人提供）：哺乳动物中枢神经系统（CNS）中表达NG2蛋白聚糖的神经胶质细胞（NG2细胞）是第四种主要的神经胶质细胞群，不同于成熟的少突胶质细胞、星形胶质细胞或静息的分枝小胶质细胞。它们在灰质和白质中分化为少突胶质细胞，并在脱髓鞘病变的发育和修复过程中提供内源性髓鞘细胞来源。虽然所有的NG2细胞都表达血小板来源的生长因子受体α和基本的螺旋-环-螺旋转录因子Olig2，但它们的命运和增殖行为存在一些区域差异。一个例子是NG2细胞在前脑背侧和腹侧的星形胶质细胞形成命运。胚胎腹侧前脑的NG2细胞亚群产生该区域40%的原生质星形胶质细胞，而背侧前脑的NG2细胞的命运仅限于少突胶质细胞谱系。研究表明，前脑腹侧和背侧的NG2细胞来自不同的生发区，这些生发区由不同的转录因子指定。特异性目的1将研究NG2细胞星形胶质细胞形成命运的背腹侧差异是否由生发区转录因子编码决定。NG2细胞异质性的另一个例子是灰质和白质中NG2细胞的增殖率和少突胶质细胞分化率的差异。已知白质中的NG2细胞比灰质中的NG2细胞经历更大的扩张和少突胶质细胞分化。我们最近的切片培养实验表明，与灰质细胞相比，白质中的NG2细胞对血小板衍生生长因子的反应更大程度上增殖。此外，在灰质而非白质中，NG2细胞的增殖通过激活钾通道家族而增加。特异性目的2将探讨在发育和髓鞘再生过程中导致灰质和白质NG2细胞增殖和少突胶质细胞分化差异的机制。

DESCRIPTION (provided by applicant): Glial cells in the mammalian central nervous system (CNS) that express the NG2 proteoglycan (NG2 cells) represent a fourth major glial cell population that is distinct from mature oligodendrocytes, astrocytes, or resting ramified microglia. They differentiate into oligodendrocytes in gray and white matter and provide an endogenous source of myelinating cells during development and repair of demyelinated lesions. While all NG2 cells express platelet-derived growth factor receptor alpha and the basic helix-loop-helix transcription factor Olig2, there are some regional differences in their fate and proliferative behavior. One example is the astrogliogenic fate of NG2 cells in the dorsal and ventral forebrain. A subpopulation of NG2 cells in the embryonic ventral forebrain generates 40% of the protoplasmic astrocytes in the region, whereas the fate of NG2 cells in the dorsal forebrain is restricted to the oligodendrocyte lineage. It has been shown that NG2 cells in the ventral and dorsal forebrain arise from distinct germinal zones that are specified by distinct transcription factors. Specific Aim 1 will investigate whether the dorsoventral differences in the astrogliogenic fate of NG2 cells are established by the transcription factor code of the germinal zone of origin. Another example of NG2 cell heterogeneity is the difference in the rate of proliferation and oligodendrocyte differentiation between NG2 cells in the gray and white matter. NG2 cells in the white matter are known to undergo greater expansion and oligodendrocyte differentiation than those in the gray matter. Our recent slice culture experiments indicate that NG2 cells in the white matter proliferate to a greater extent in response to platelet-derived growth factor compared with their gray matter counterparts. Furthermore, proliferation of NG2 cells in the gray but not white matter is increased by activation of a family of potassium channels. Specific Aim 2 will investigate the mechanisms that lead to differences in proliferation and oligodendrocyte differentiation of NG2 cells in gray and white matter during development and remyelination.