M2 microglia promotes neurogenesis and oligodendrogenesis from neural stem/progenitor cells via the PPARγ signaling pathway

// Jichao Yuan 1, 2 , Hongfei Ge 1 , Wei Liu 1 , Haitao Zhu 1 , Yaxing Chen 1 , Xuan Zhang 1 , Yang Yang 1 , Yi Yin 1 , Weixiang Chen 1 , Wanjiang Wu 1 , Yunfeng Yang 1 , Jiangkai Lin 1 1 Department of Neurosurgery and Key Laboratory of Neurotrauma, Southwest Hospital, Third Military Medical University, Chongqing 400038, China 2 Department of Neurology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China Correspondence to: Jiangkai Lin, email: jklin@tmmu.edu.cn Keywords: NSPCs, differentiation, M2 microglia, 15d-PGJ2, PPARγ Received: May 17, 2016      Accepted: January 23, 2017      Published: February 28, 2017 ABSTRACT 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-PGJ 2 , 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.