Homeostatic regulation of NG2 cell dynamics

项目摘要-NG 2细胞动力学的稳态调节 NG 2细胞代表哺乳动物中枢神经系统中的第四大神经胶质细胞群。 神经干细胞是不同于神经干细胞、成熟少突胶质细胞、星形胶质细胞或小胶质细胞的系统。 它们产生少突胶质细胞，因此是髓鞘再生细胞的重要来源。他们 对少突胶质细胞系细胞或髓磷脂密度的变化作出强烈反应， 在神经系统中制造正确数量的髓鞘所需的正确数量的少突胶质细胞 网络它们高度整合在神经网络中，不仅在细胞之间相互作用， 少突胶质细胞谱系，但也与神经元和其他神经胶质细胞。拟议项目将 探讨反馈信号维持少突胶质细胞稳态的机制 和髓磷脂。在目标1中，我们将测试小胶质细胞在调节神经元的功能中发挥关键作用的假设。 NG 2细胞密度在正常生理条件下，以及在髓鞘再生。在目标2中， 我们将检验Hippo信号传导介导NG 2细胞密度依赖性 髓鞘和NG 2之间的细胞粘附分子和外泌体信号传导 细胞向NG 2细胞提供反馈信号，NG 2细胞调节少突胶质细胞分化。这些 假设是基于系统分析和特定细胞研究的结果。的 这项研究的结果将通过建立基本的新原则来增进我们的知识 与少突胶质细胞系细胞内稳态调节的内在和外在机制有关 少突胶质细胞和髓磷脂在其他细胞成分的背景下。

Project summary – Homeostatic regulation of NG2 cell dynamics NG2 cells represent a fourth major glial cell population in the mammalian central nervous system that is distinct from neural stem cells, mature oligodendrocytes, astrocytes, or microglia. They generate oligodendrocytes and hence are an important source of remyelinating cells. They respond robustly to changes in the density of oligodendrocyte lineage cells or myelin and restore the correct number of oligodendrocytes needed to make the correct amount of myelin in the neural network. They are highly integrated in the neural network and interact not only among the cells in the oligodendrocyte lineage but also with neurons and other glia. The proposed project will investigate the mechanism of feedback signaling that maintains homeostasis of oligodendrocytes and myelin. In Aim 1, we will test the hypothesis that microglia play a critical role in regulating NG2 cell density under normal physiological conditions, as well as during remyelination. In Aim 2, we will test the hypotheses that the Hippo signaling mediates NG2 cell density-dependent proliferation and that cell adhesion molecules and exosome signaling between myelin and NG2 cells provide feedback signaling to NG2 cells that regulates oligodendrocyte differentiation. These hypotheses are based on findings from both systems analyses and specific cellular studies. The outcome of the study will advance our knowledge by establishing fundamental new principles related to oligodendrocyte lineage cell intrinsic and extrinsic mechanisms of homeostatic regulation of oligodendrocytes and myelin in the context of other cellular constituents.