Melchiorri Daniela, Cappuccio Irene, Ciceroni Cinzia, Spinsanti Paola, Mosillo Paola, Sarichelou Iran, Sale Patrizio, Nicoletti Ferdinando
Department of Human Physiology and Pharmacology, University of Rome La Sapienza, Rome, Italy.
Neuropharmacology. 2007 Sep;53(4):473-80. doi: 10.1016/j.neuropharm.2007.05.031. Epub 2007 Jun 29.
Functional mGlu receptor subtypes are found in stem/progenitor cells, and regulate proliferation, differentiation, and survival of these cells. Activation of mGlu5 receptors supports self-renewal of embryonic stem cells, which are pluripotent cells isolated from the blastocyst capable of generating all the body's cell lineages, including germ cells. Differentiation of embryonic stem cells into embryoid bodies is associated with the induction of mGlu4 receptors, the activation of which drives cell differentiation towards the mesoderm and endoderm lineages. Different mGlu receptor subtypes, mGlu3 and mGlu5 receptors in particular, are found in neural stem cells (stem cells resident in the CNS that give rise to neurons, astrocytes or oligodendrocytes) isolated from the developing brain or from regions of persistent neurogenesis of the adult brain (e.g. the subventricular zone lining the wall of the lateral ventricles). The evidence that activation of mGlu3 and mGlu5 receptors stimulates proliferation of these cells is particularly interesting because of the similarities between neural stem cells and putative cancer stem cells that support the growth of malignant gliomas. A link among mGlu receptors, stem cells and cancer is supported by the finding that mGlu4 receptors are expressed by cerebellar granule cell neuroprogenitors, which are the putative cells of origin of medulloblastomas. The study of mGlu receptors in stem/progenitor cells has potential applications in the optimisation of protocols of cell expansion and differentiation aimed at cell replacement strategies, and may gain new insights into the pathophysiology of neurodevelopmental disorders and brain tumours.
功能性代谢型谷氨酸受体亚型存在于干细胞/祖细胞中，并调节这些细胞的增殖、分化和存活。代谢型谷氨酸5受体的激活支持胚胎干细胞的自我更新，胚胎干细胞是从囊胚中分离出来的多能细胞，能够产生包括生殖细胞在内的身体所有细胞谱系。胚胎干细胞分化为类胚体与代谢型谷氨酸4受体的诱导有关，其激活驱动细胞向中胚层和内胚层谱系分化。不同的代谢型谷氨酸受体亚型，特别是代谢型谷氨酸3和代谢型谷氨酸5受体，存在于从发育中的大脑或成人大脑持续神经发生区域（如侧脑室壁内衬的室下区）分离出的神经干细胞（中枢神经系统中驻留的干细胞，可产生神经元、星形胶质细胞或少突胶质细胞）中。代谢型谷氨酸3和代谢型谷氨酸5受体的激活刺激这些细胞增殖的证据尤其有趣，因为神经干细胞与支持恶性胶质瘤生长的假定癌症干细胞之间存在相似性。代谢型谷氨酸受体、干细胞和癌症之间的联系得到了以下发现的支持：代谢型谷氨酸4受体由小脑颗粒细胞神经祖细胞表达，而小脑颗粒细胞神经祖细胞是髓母细胞瘤的假定起源细胞。对干细胞/祖细胞中代谢型谷氨酸受体的研究在优化旨在细胞替代策略的细胞扩增和分化方案方面具有潜在应用，并可能为神经发育障碍和脑肿瘤的病理生理学提供新的见解。
