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  • GABAA receptors GABAAR are heteropentameric ion channels wit

    2018-11-08

    GABAA receptors (GABAAR) are heteropentameric ion channels with prevalent expression on immature cells, including astrocyte-like SVZ cells, TACs and neuroblasts purchase Myoseverin (Platel et al., 2010). Previous studies reveal that GABAAR activation decreases the proliferation of embryonic neocortical progenitors (Haydar et al., 2000; LoTurco et al., 1995; Wang et al., 2003), early postnatal neural progenitors (Nguyen et al., 2003) and adult NSCs and TACs (Fernando et al., 2011; Liu et al., 2005). In the SVZ, GABA produced by neuroblasts exerts a feedback mechanism inhibiting the proliferation of astrocyte-like SVZ cells (Liu et al., 2005). The inhibition of GABAAR signaling resulting from an endogenous expression of Diazepam binding inhibitor in TACs stimulates their proliferation in the early postnatal SVZ (Alfonso et al., 2012). Downstream GABA signaling in NSCs has been linked to histone H2AX phosphorylation, which limits proliferation (Fernando et al., 2011); however, the effects of GABA signaling on NSC exiting quiescence or in the activation of NSCs have yet to be determined. Further investigations are warranted to identify whether perturbations of GABA neurotransmitter signaling upon injury impact the recruitment and proliferation of NSCs.
    Materials and methods
    Results
    Discussion Here, we report on a FACS method that is able to prospectively sort quiescent NSCs with a LeXbright phenotype and to distinguish them from their proliferating counterparts. Using a dynamic model of neurogenic niche restoration in the adult mouse SVZ, we show that quiescent NSCs, in contrast to their proliferating counterparts, are able to resist to gamma-radiation and then enter the purchase Myoseverin rapidly after exposure, allowing efficient recovery of neurogenesis for long term. In addition, we demonstrate that the decrease in GABAAR signaling resulting from the depletion of neuroblasts, the major GABA source in the SVZ, allowed quiescent NSCs to enter the cell cycle in the irradiated brain. Therefore, our study identifies GABAAR signaling as a mechanism for controlling the size of the NSC niche through the regulation of NSC quiescence.
    Conclusions
    Author contributions
    Acknowledgments
    M.D. has a fellowship from La Ligue Contre le Cancer and J.R.P. from Région Ile-de-France (DIM STEM-Pôle). This work was supported by grants of ANR-SEST (Neurorad), INCA (Tetratips) and Electricité de France (EDF). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
    Introduction Although bone tissue engineering offers a valid alternative to current bone autograft and allograft surgeries, the repair of skeletal defects still represents a substantial economic and biomedical burden (Conrad and Huss, 2005). Tissue engineering strategies for the replacement of load-bearing tissues require a combination of a scaffold, a source of bone forming cells, and growth factors (Langer and Vacanti, 1993). Native bone forming cells, osteoblasts, are typically difficult to isolate and to expand in vitro (Declercq et al., 2004). A stem cell population with an osteogenic potential would be preferred. Bone marrow-derived stromal cells (BMSCs, also known as bone marrow-derived mesenchymal stem cells), which have been long used for bone tissue engineering applications, require specialized harvesting and purification procedures and their presence is also reduced in aged bone marrow (Caplan, 2004). Amniotic fluid was described by De Coppi et al. (2007) as a new source of stem cells, which can be directed into the three primary embryonic lineages of mesoderm, ectoderm and definitive endoderm. Amniotic fluid-derived stem cells (AFSCs) are easily accessible and readily available from amniocentesis samples that would be otherwise discarded. AFSCs may approach the plasticity degree of embryonic stem cells, but their use in regenerative medicine does not present disadvantages such as ethic controversies, the risk of teratoma formation and the need of a feeder layer to grow.