Heterogeneity of NG2 Glial Cells

NG2 胶质细胞的异质性

基本信息

批准号：
8662817
负责人：
Akiko Nishiyama
金额：
$ 33.85万
依托单位：
UNIVERSITY OF CONNECTICUT STORRS
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-01 至 2017-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8662817
关键词：
Affect Astrocytes Axon BHLH Protein Behavior Brain CSPG4 gene Cell Proliferation Cells Code Commit Demyelinations Development Dorsal Embryo Exhibits FLP recombinase Family Future Genetic Genetic Transcription Gray unit of radiation dose Heterogeneity Lateral Lead Lesion Maps Medial Microglia Mitogens Multiple Sclerosis Mus NG2 antigen Neuraxis Neuroglia Neurons Oligodendroglia PDGF-AA PDGFRB gene Physiological Platelet-Derived Growth Factor Platelet-Derived Growth Factor alpha Receptor Population Potassium Channel Proliferating Prosencephalon Protoplasmic Astrocyte Recording of previous events Reporter Rest Signal Pathway Slice Source Specific qualifier value Surface Antigens Transplantation Ventricular base cell type gray matter homeodomain in vivo nerve stem cell oligodendrocyte lineage postnatal precursor cell progenitor protein expression regional difference remyelination repaired research study response tool transcription factor voltage white matter

项目摘要

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.

描述（由申请人提供）：表达NG2蛋白聚糖（NG2细胞）的哺乳动物中枢神经系统（CNS）中的神经胶质细胞代表了与成熟的少突胶质细胞，星形胶质细胞或静止的稀有小胶质细胞不同的第四个主要神经胶质细胞群。它们分化为灰色和白质中的少突胶质细胞，并在开发和修复脱髓鞘病变期间提供了内源性细胞的内源性来源。尽管所有NG2细胞表达了血小板衍生的生长因子受体α和基本的螺旋 - 环螺旋转录因子Olig2，但其命运和增殖行为存在一些区域差异。一个例子是背侧和腹前脑NG2细胞的星形胶质命运。 NG2细胞在胚胎腹前脑中的亚群产生该区域的原生质星形胶质细胞的40％，而背侧前脑中NG2细胞的命运仅限于少突胶质细胞线。已经表明，腹前脑和背侧前脑中的NG2细胞由不同的生发区域引起，这些生发区域由不同的转录因子指定。具体的目标1将研究NG2细胞的星形胶质生成命运的背腹差异是否通过生发原点的转录因子代码建立。 NG2细胞异质性的另一个例子是灰质和白质NG2细胞之间增殖和少突胶质细胞分化的速率差异。已知白质中的NG2细胞比灰质中的NG2细胞经历更大的膨胀和少突胶质细胞分化。我们最近的切片培养实验表明，与血小板衍生的生长因子相比，白质中的NG2细胞在更大程度上增殖。此外，通过激活钾通道的激活增加了灰色但不是白质的NG2细胞的增殖。具体目标2将研究导致在发育和透明化过程中灰色和白质中NG2细胞增殖和少突胶质细胞分化差异的机制。