Heterogeneity of NG2 Glial Cells

描述（由申请方提供）：哺乳动物中枢神经系统（CNS）中表达NG 2蛋白聚糖的神经胶质细胞（NG 2细胞）代表第四种主要神经胶质细胞群，与成熟少突胶质细胞、星形胶质细胞或静息分枝小胶质细胞不同。它们分化成灰色和白色物质中的少突胶质细胞，并在脱髓鞘病变的发展和修复过程中提供髓鞘形成细胞的内源性来源。虽然所有NG 2细胞表达血小板衍生生长因子受体α和碱性螺旋-环-螺旋转录因子Olig 2，但它们的命运和增殖行为存在一些区域差异。一个例子是NG 2细胞在背侧和腹侧前脑中的星形胶质细胞的命运。NG 2细胞在胚胎腹侧前脑的亚群产生40%的原生质星形胶质细胞在该地区，而NG 2细胞在背侧前脑的命运是有限的少突胶质细胞谱系。已经表明，腹侧前脑和背侧前脑中的NG 2细胞来自由不同的转录因子指定的不同的生发区。具体目标1将研究NG 2细胞的星形胶质细胞命运的背腹侧差异是否是由起源于生发区的转录因子编码建立的。NG 2细胞异质性的另一个例子是灰质和白色物质中NG 2细胞之间的增殖速率和少突胶质细胞分化的差异。已知白色物质中的NG 2细胞比灰质中的NG 2细胞经历更大的扩增和少突胶质细胞分化。我们最近的切片培养实验表明，NG 2细胞在白色物质增殖到更大的程度，以响应血小板衍生的生长因子相比，他们的灰质同行。此外，NG 2细胞在灰色而非白色物质中的增殖通过钾通道家族的激活而增加。具体目标2将研究导致发育和髓鞘再生过程中灰质和白色物质中NG 2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.