We have discovered a population of immature nestin-positive precursors with neural differentiation potential residing in the meninges of the brain and the spinal cord. In this work, we asked whether these precursors were developmentally conserved in meninges from embryo to adult. Changes in distribution and in the expression of cellular and extracellular matrix antigens were analyzed in meninges from embryo (E14, E20), perinatal (P0, P15) and adult rats by laser capture microscopy, rtPCR, FACS and confocal microscopy. We found cells expressing the stem cell marker nestin in meninges as early as E14. The number, density and proliferation rate of these cells significantly decreased with the animal age and were 13.3±4.4% of the adult rat brain meningeal cells. Vimentin, DCX and Tuj1 positive cells were present in meninges in all developmental stages. Nestin-positive cells were in tight contact with several extracellular matrix components including laminin, fibronectin and heparin sulphate. We also assessed the in vitro stem cell properties of meningeal nestin-positive cells. As expected from the ex-vivo observation, the number of colony forming unit (CFU) and cell growth rate decreased with rat age. Under differentiating conditions, nestin-positive cells expanded from rats of any age underwent neural differentiation. The in vitro-generated neurons displayed neuronal morphology and phenotype, formed synapses and displayed electrophysiological responses to depolarizing agents. We conclude that meninges are a stem cell niche capable of housing a population of stem/progenitor cells with neural differentiation potential and persisting in adult brain. This suggests that meninges are involved in adult neurogenesis.
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