Homeostatic regulation of NG2 cell dynamics

项目总结-NG2细胞动力学的动态平衡调节 NG2细胞是哺乳动物中枢神经系统中的第四大神经胶质细胞群 有别于神经干细胞、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，因此是重新髓鞘细胞的重要来源。他们 对少突胶质细胞系细胞或髓鞘密度的变化做出强有力的反应并恢复 在神经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。它们高度集成在神经网络中，不仅在 少突胶质细胞的谱系还包括神经元和其他胶质细胞。拟议的项目将 探讨反馈信号维持少突胶质细胞动态平衡的机制 还有髓磷脂。在目标1中，我们将检验小胶质细胞在调节中起关键作用的假设。 NG2细胞密度在正常生理条件下，以及在重新髓鞘形成过程中。在目标2中， 我们将测试河马信号介导NG2细胞密度依赖的假设 髓鞘和NG2之间的增殖与细胞黏附分子和外切体信号转导 细胞向NG2细胞提供反馈信号，调节少突胶质细胞的分化。这些 假说是基于系统分析和特定细胞研究的结果。这个 研究的结果将通过建立基本的新原则来促进我们的知识 与少突胶质细胞谱系有关的细胞内、外稳态调节机制 少突胶质细胞和髓鞘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.