Metabotropic glutamate receptors in stem/progenitor cells

Daniela Melchiorri, Irene Cappuccio, Cinzia Ciceroni, Paola Spinsanti, Paola Mosillo, Iran Sarichelou, Patrizio Sale, Ferdinando Nicoletti

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)473-480
Number of pages8
JournalNeuropharmacology
Volume53
Issue number4
DOIs
Publication statusPublished - Sep 2007

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Keywords

  • Embryonic stem cells
  • Metabotropic glutamate receptor
  • Neural progenitor cells

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

Cite this

Melchiorri, D., Cappuccio, I., Ciceroni, C., Spinsanti, P., Mosillo, P., Sarichelou, I., Sale, P., & Nicoletti, F. (2007). Metabotropic glutamate receptors in stem/progenitor cells. Neuropharmacology, 53(4), 473-480. https://doi.org/10.1016/j.neuropharm.2007.05.031