The role of astrocytes on glutamate release and differentiation of glioma stem cells (GSCs) remains unknown. We investigated glutamate release, proliferation, and differentiation of GSCs after indirect incubation with astrocytes in vitro, including morphology change, GFAP expression, glutamine synthetase, and EAAT1 expression. The role of formyl peptide receptor (FPR) agonist and antagonist on interaction between astrocytes and GSCs in co-culture model was analyzed. We found: (1) After incubation of astrocytes and GSCs, differentiated GSCs present the morphology of astrocytes and express GFAP. (2) GSCs release high concentration of glutamate, as well as tumor cells. However, differentiated GSCs possess the ability of glutamate uptake. (3) Proliferation ability of differentiated GSCs is lower than tumor cells. (4) Glutamine synthetase is predominantly expressed in the nucleus of tumor cells, while in the cytoplasm of differentiated GSCs. (5) Differentiation of GSCs could be triggered by FPR agonist, while astrocyte-induced differentiation of GSCs could be blocked by FPR antagonist. These results indicate astrocytes promote astrocytic differentiation and glutamate uptake of GSCs via FPR.

星形胶质细胞对胶质瘤干细胞 (GSCs) 谷氨酸释放和分化的作用仍然未知。我们研究了在体外与星形胶质细胞间接孵育后 GSCs 的谷氨酸释放、增殖和分化，包括形态变化、GFAP 表达、谷氨酰胺合成酶和 EAAT1 表达。分析了共培养模型中甲酰肽受体（FPR）激动剂和拮抗剂对星形胶质细胞和GSCs相互作用的作用。我们发现：（1）星形胶质细胞和GSCs孵育后，分化的GSCs呈现星形胶质细胞的形态并表达GFAP。(2) GSCs 释放高浓度的谷氨酸，以及肿瘤细胞。然而，分化的GSCs具有吸收谷氨酸的能力。(3)分化后的GSCs增殖能力低于肿瘤细胞。(4)谷氨酰胺合成酶主要在肿瘤细胞的细胞核中表达，而在分化的GSCs的细胞质中表达。(5) FPR激动剂可触发GSCs分化，而FPR拮抗剂可阻断星形胶质细胞诱导的GSCs分化。这些结果表明星形胶质细胞通过 FPR 促进 GSCs 的星形胶质细胞分化和谷氨酸摄取。