Abstract
Neural stem cells are fundamental to development of the central nervous system (CNS)—as well as its plasticity and regeneration—and represent a potential tool for neuro transplantation therapy and research. This study is focused on examination of the proliferation dynamic and fate of embryonic neural stem cells (eNSCs) under differentiating conditions. In this work, we analyzed eNSCs differentiating alone and in the presence of sonic hedgehog (SHH) or triiodothyronine (T3) which play an important role in the development of the CNS. We found that inhibition of the SHH pathway and activation of the T3 pathway increased cellular health and survival of differentiating eNSCs. In addition, T3 was able to increase the expression of the gene for the receptor smoothened (Smo), which is part of the SHH signaling cascade, while SHH increased the expression of the T3 receptor beta gene (Thrb). This might be the reason why the combination of SHH and T3 increased the expression of the thyroxine 5-deiodinase type III gene (Dio3), which inhibits T3 activity, which in turn affects cellular health and proliferation activity of eNSCs.
Highlights
Embryonic neural stem cells give rise to almost all cell types found in the central nervous system (CNS), they play an important role in brain development
The data represents an average from six experiments and the error bars represent ± SEM
The final number of cells in all treatments was not significantly different, T3 and the sonic hedgehog (SHH) inhibitor PF-5274857 hydrochloride (PF)-5274857 increased the cellular health of differentiating Embryonic neural stem cells (eNSCs) measured by the MTS assay. This suggests that enhanced T3 and/or suppressed SHH signaling might improve cellular health of the stem cells
Summary
Embryonic neural stem cells (eNSCs) give rise to almost all cell types found in the central nervous system (CNS), they play an important role in brain development. ENSCs represent a useful tool for development of neurotransplantation therapy for neurological diseases. The fate of both endogenous and grafted eNSCs is regulated by many factors that control their survival, proliferation and differentiation. On the other hand, targeted modulation of the level of these information molecules might have therapeutic value in some neurological diseases or might be used to pre-treat the cells in vitro before engraftment to enhance their survival and ensure adequate differentiation which still hinders the development of successful transplantation therapies [1,2,3]. We analyzed eNSCs differentiating alone and in the presence of two important factors, sonic hedgehog and triiodothyronine
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