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.
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The study was supported by Young and Middle-aged Backbone Key Research Project of National Health and Family Planning Commission of Fujian Province (No. 2017-ZQN-46 to Pei-Sen Yao), National Natural Science Foundation of China (No. 81802492 to Pei-Sen Yao), Natural Science Funding of Fujian Province (No. 2018J01175 to Pei-Sen Yao).
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Xu, Y., Yang, J., Kang, D. et al. Astrocytes Regulate Differentiation and Glutamate Uptake of Glioma Stem Cells via Formyl Peptide Receptor. Cell Mol Neurobiol (2020). https://doi.org/10.1007/s10571-020-00886-3