Endogenous activation of mGlu5 metabotropic glutamate receptors supports self-renewal of cultured mouse embryonic stem cells

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• 作者：Irene Cappuccio ; Paola Spinsanti ; Antonio Porcellini ; Francesca Desiderati ; Teresa De Vita ; Marianna Storto ; Loredana Capobianco ; Giuseppe Battaglia ; Ferdin ; o Nicoletti ; Daniela Melchiorri
• 关键词：mGlu receptors ; Embryonic stem cells ; Self-renewal ; Oct-4 ; Nanog
• 刊名：Neuropharmacology
• 出版年：2005
• 出版时间：2005
• 年：2005
• 卷：49
• 期：Supplement 1
• 页码：196-205
• 全文大小：521 K

文摘

Cultured mouse embryonic stem (ES) cells maintained under undifferentiated conditions (i.e. grown in medium containing 15 % FCS and leukemia inhibitory factor – LIF) expressed mGlu5 metabotropic glutamate receptors. Activation of these receptors with quisqualate increased [Ca²⁺]_i but only when cultures were deprived of extracellular glutamate, indicating that the receptor was saturated by the endogenous glutamate. Pharmacological blockade of mGlu5 receptors with 2-methyl-6-(phenylethynyl)pyridine (MPEP) or antisense-induced knock-down of mGlu5 receptors decreased the expression of the two main transcription factors that sustain ES cell self-renewal, i.e. Oct-4 and Nanog, as assessed by real-time PCR and immunoblotting. Exposure of ES cell cultures to MPEP also reduced alkaline phosphatase activity, a marker of undifferentiated ES cells. These data support a critical role for mGlu receptors in early development showing that mGlu5 receptors are expressed by ES cells and their activation sustains ES cell self-renewal in culture.