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-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.
Highlights
Neural stem/progenitor cells (NSPCs) have a strong capacity for self-proliferation and differentiation
Our study discovers that, when induced by anti-inflammatory M2 microglia supernatant, NSPCs differentiated significantly more into neurons and oligodendrocytes and less into astrocytes
Our research confirm that M2 microglia can promote neurogenesis and oligodendrogenesis from NSPCs differentiation through the PPARγ pathway
Summary
Neural stem/progenitor cells (NSPCs) have a strong capacity for self-proliferation and differentiation. They have great potential for use as replacement cells and play an important role in neural repair after central nervous system (CNS) injury [1]. It is of great importance to find an effective way to promote neurogenesis and oligodendrogenesis from NSPCs differentiation. Inflammation is a key factor affecting NSPCs differentiation [5]. As resident immune cell in the CNS, microglia can be rapidly activated after injury, and participate in local inflammatory reaction [6]. It has been reported that microglia activated by IL-4 can promote neurogenesis and oligodendrogenesis from NSPCs differentiation [12], but the specific mechanism of action is unclear
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