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The generation of human induced pluripotent stem cells (iPSCs) holds great promise for the development of regenerative medicine therapies to treat a wide range of human diseases. However, the generation of iPSCs in the absence of integrative DNA vectors remains problematic. Here, we report a simple, highly reproducible RNA-based iPSC generation approach that utilizes a single, synthetic self-replicating VEE-RF RNA replicon that expresses four reprogramming factors (OCT4, KLF4, and SOX2, with c-MYC or GLIS1) at consistent high levels prior to regulated RNA degradation. A single VEE-RF RNA transfection into newborn or adult human fibroblasts resulted in efficient generation of iPSCs with all the hallmarks of stem cells, including cell surface markers, global gene expression profiles, and in vivo pluripotency, to differentiate into all three germ layers. The VEE-RF RNA-based approach has broad applicability for the generation of iPSCs for ultimate use in human stem cell therapies in regenerative medicine.

Kainate receptors assembled with the GluR6 subunit are significant for both the sensitivity of CA3 neurons to kainate and for synaptic transmission at the mossy fibre-CA3 synapse, according to research using mutant mice lacking the kainate-receptor subunit GluR6. It was established that GluR6-deficient mice are less susceptible to systemic administration of kainate. This research indicates a vital role for kainate receptors, rather than alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors, in kainate-induced seizures and excitoxic neuronal death in the hippocampus.