M2 microglia promotes neurogenesis and oligodendrogenesis from neural stem/progenitor cells via the PPARγ signaling pathway.
M2 microglia promotes neurogenesis and oligodendrogenesis from neural stem/progenitor cells via the PPARγ signaling pathway.
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M2 小胶质细胞通过 PPAR 信号通路促进神经干/祖细胞的神经发生和少突胶质细胞发生。
DOI：
10.18632/oncotarget.15774
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发表时间：
2017-03-21
期刊：
影响因子：
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通讯作者：
Lin J
中科院分区：
文献类型：
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作者：
Yuan J;Ge H;Liu W;Zhu H;Chen Y;Zhang X;Yang Y;Yin Y;Chen W;Wu W;Yang Y;Lin J
神经干/祖细胞是神经损伤后细胞替代治疗的重要细胞来源。如何诱导神经干细胞向神经元和少突胶质细胞分化是神经科学研究中的一个具有挑战性的问题。在本研究中，我们将小胶质细胞分化为M1和M2表型，用其上清液诱导NSPC分化，并探讨不同表型对NSPC分化的影响及其机制。我们发现，在M1表型培养上清液作用下，NSPC分化为较少的Tuj-1+和Orig2+细胞，但分化为更多的GFAP+细胞。同时，M2小胶质细胞培养上清液诱导NSPC分化后，Tuj-1+和Opol2+细胞数量明显增加，GFAP+细胞数量减少。我们还观察到PPARγ的内源性配体15d-PgJ2在M2表型培养上清液中升高，并能激活NSPC中PPARγ的表达，而使用PPARγ抑制剂GW9662可以降低分化的神经元和少突胶质细胞的比例。我们的研究结果证实，M2小胶质细胞上清液可以激活PPARγ信号通路，促进神经发生和NSPC分化为少突胶质细胞。本研究为NSPC定向分化的诱导提供了进一步的理论依据。
Neural stem/progenitor cells (NSPCs) are an important source of cells for cell replacement therapy after nerve injury. How to induce NSPCs differentiation towards neurons and oligodendrocytes is a challenging issue in neuroscience research. In the present study, we polarized microglia into M1 and M2 phenotype, used their supernatants to induce NSPCs differentiation, and investigated the effects of different microglia phenotypes on NSPCs differentiation and their mechanisms. We discovered that, after exposure to M1 phenotype supernatant, NSPCs differentiated into fewer Tuj-1+ and Olig2+ cells, but more GFAP+ cells. Meanwhile, a significantly increased number of Tuj-1+ and Olig2+ cells and smaller number of GFAP+ cells were generated by M2 microglia supernatant-induced NSPCs differentiation. We also observed that 15d-PGJ2, an endogenous ligand of PPARγ, was elevated in M2 phenotype supernatant and could activate PPARγ expression in NSPCs, whereas use of the PPARγ inhibitor GW9662, could reduce the percentage of differentiated neurons and oligodendrocytes. Our study results confirm that M2 microglia supernatant can activate the PPARγ signaling pathway and promote neurogenesis and oligodendrogenesis from NSPCs differentiation. The present study provides a further theoretical basis for induction of NSPCs oriented differentiation.