SummarySchwann cells play a crucial role in successful nerve repair and regeneration by supporting both axonal growth and myelination. However, the sources of human Schwann cells are limited both for studies of Schwann cell development and biology and for the development of treatments for Schwann cell-associated diseases. Here, we provide a rapid and scalable method to produce self-renewing Schwann cell precursors (SCPs) from human pluripotent stem cells (hPSCs), using combined sequential treatment with inhibitors of the TGF-β and GSK-3 signaling pathways, and with neuregulin-1 for 18 days under chemically defined conditions. Within 1 week, hPSC-derived SCPs could be differentiated into immature Schwann cells that were functionally confirmed by their secretion of neurotrophic factors and their myelination capacity in vitro and in vivo. We propose that hPSC-derived SCPs are a promising, unlimited source of functional Schwann cells for treating demyelination disorders and injuries to the peripheral nervous system.

In this paper, we present novel OLED display technologies for large-size UHD OLED TVs, including an IGZO TFT backplane, an RGBW pixel structure with white OLED, driving schemes and compensation methods applied to the panel. We also discuss technical issues and challenges in panel design and driving methods to compensate non-uniformities of oxide TFTs, OLED devices, color, and luminance. Using these technologies, we have successfully launched 55-, 65-and 77- inch UHD OLED TVs. Currently we focus on technologies to achieve higher image qualities, a wider color range and a higher cost competitiveness in the TV market.

The direct lineage reprogramming of somatic cells to other lineages by defined factors has led to innovative cell-fate-change approaches for providing patient-specific cells. Recent reports have demonstrated that four pluripotency factors (Oct4, Sox2, Klf4, and c-Myc) are sufficient to directly reprogram fibroblasts to other specific cells, including induced neural stem cells (iNSCs). Here, we show that mouse fibroblasts can be directly reprogrammed into midbrain dopaminergic neuronal progenitors (DPs) by temporal expression of the pluripotency factors and environment containing sonic hedgehog and fibroblast growth factor 8. Within thirteen days, self-renewing and functional induced DPs (iDPs) were generated. Interestingly, the inhibition of both Jak and Gsk3β notably enhanced the iDP reprogramming efficiency. We confirmed the functionality of the iDPs by showing that the dopaminergic neurons generated from iDPs express midbrain markers, release dopamine, and show typical electrophysiological profiles. Our results demonstrate that the pluripotency factors-mediated direct reprogramming is an invaluable strategy for supplying functional and proliferating iDPs and may be useful for other neural progenitors required for disease modeling and cell therapies for neurodegenerative disorders.

Previously, we reported the phosphorylation of moesin induced by electroconvulsive shock in rat brain and by glutamate in immortalized rat hippocampal cells. However, the function of phosphorylated moesin in differentiated neurons is not well understood. In this study, we observed that glutamate induces phosphorylation of ezrin/radixin/moesin proteins (ERM) in cultured hippocampal cells and that phosphorylated ERM localizes at the newly formed filopodia of neurites. The glutamate-induced phosphorylation of ERM is calcium-dependent, and inhibition of protein kinase C abolishes ERM phosphorylation as well as RhoA activation. The inhibitions of RhoA and RhoA kinase also diminishes the glutamate-induced ERM phosphorylation in cultured hippocampal cells. The knock-down of moesin or the inhibition of ERM phosphorylation results in the reduction of glutamate-induced filopodia protrusion and diminishes the increase in active synaptic boutons induced by glutamate treatment. These results indicate that glutamate-induced phosphorylation of ERM proteins in primary cultured differentiated hippocampal neurons is mediated by calciumdependent protein kinase C, RhoA and RhoA kinase, and the phosphorylated ERM protein is necessary for the formation of filopodial protrusion and may be involved in pre-synaptic trafficking. Keywords: calcium, ERM, filopodia, glutamate, phosphorylation, PKC. Activated ERM proteins are able to cross-link the actin cytoskeleton to the plasma membrane and influence cell morphogenesis, motility, adhesion and signaling pathways (Louvet-Vallee 2000;Bretscher et al. 2002;Ivetic and Ridley 2004). These functions of ERM proteins have been mainly demonstrated in leukocytes or epithelial cells. However, some roles of ERM proteins in neuronal cells have been described. ERM proteins have been shown to interact with the axonal cellular adhesion molecule L1 (Dickson et al. 2002), which is involved in neuronal development and the regenerative response to injury (Haas et al. 2004). In addition, ERM proteins have been shown to mediate dendritic filopodia formation in primary cultured hippocampal neurons (Furutani et al. 2007). Most of these studies have focused on developing neurons and not on the molecular mechanisms of ERM phosphorylation, although ERM proteins are present and are reactive to some stimuli in the adult brain as well as in young neurons. Much is still unknown about the biological roles of ERM proteins in the CNS.In the present study, we demonstrate that glutamateinduced ERM phosphorylation in differentiated hippocampal neuron is localized in the filopodia of neurites and results in filopodial protrusions. We also suggest that phosphorylated ERM proteins in differentiated neuron may be involved in glutamate receptor-mediated synaptic plasticity. MethodsPrimary hippocampal cell cultures Neuronal cultures were prepared from embryonic day-18 SpragueDawley rat brain, as described previously (Brewer et al. 1993) (see Appendix S1). Over 95% of the cultured cells were immunoreactive to neuron-specific...

We present a novel OLED display panel with high-reliability integrated gate driver circuit using IGZO TFTs. Our gate driver circuit can drive a large-sized OLED display not only for displaying images but also for sensing TFT characteristics for external compensation. It functions correctly even when the threshold voltage of TFTs is negative by reducing leakage currents. We have achieved a life time longer than 60,000 hours in a reliability test and successfully applied it to 55-inch UHD, 65-inch UHD and 55-inch FHD OLED displays, which improves cost-competitiveness of OLED displays against LCDs.

Spliceosomes are the core host of pre-mRNA splicing, allowing multiple protein isoforms to be produced from a single gene. Herein, we reveal that spliceosomes are more abundant in human pluripotent stem cells (hPSs), including human embryonic stem cells (hESs) and human induced pluripotent stem cells (hiPSs), than non-hPSs, and their presence is associated with high transcriptional activity. Supportively, spliceosomal components involved in the catalytically active pre-mRNA splicing step were mainly co-localized with hPS spliceosomes. By profiling the gene expression of 342 selected splicing factors, we found that 71 genes were significantly altered during the reprogramming of human somatic cells into hiPSs. Among them, SNRPA1, SNRPD1, and PNN were significantly up-regulated during the early stage of reprogramming, identified as hub genes by interaction network and cluster analysis. SNRPA1, SNRPD1, or PNN depletion led to a pronounced loss of pluripotency and significantly blocked hiPS generation. SNRPA1, SNRPD1, and PNN co-localized with the hPS spliceosomes, physically interacted with each other, and positively influenced the appearance of hPS spliceosomes. Our data suggest that SNRPA1, SNRPD1, and PNN are key players in the regulation of pluripotency-specific spliceosome assembly and the acquisition and maintenance of pluripotency.

The world's first 77-inch UHD OLED TV with an excellent image quality has been developed, using an IGZO TFT backplane and white OLEDs with an RGBW pixel structure and a novel compensation method applied to the panel. In this paper, we discuss technical issues and challenges in panel design and driving methods to compensate the non-uniformity of oxide TFTs, OLED devices, colors, and luminance, including our recent technologies that have realized a panel size scalability and a product reliability for commercializing large-size OLED TVs.

Background Schwann cells (SCs) are primarily responsible for regeneration and repair of the peripheral nervous system (PNS). Renewable and lineage-restricted SC precursors (SCPs) are considered highly desirable and promising cell sources for the production of SCs and for studies of SC lineage development, but SCPs are extremely limited. Here, we present a novel direct conversion strategy for the generation of human SCPs, capable of differentiating into functional SCs. Methods Easily accessible human skin fibroblast cells were directly induced into integration-free SCPs using episomal vectors (Oct3/4, Klf4, Sox2, L-Myc, Lin28 and p53 shRNA) under SCP lineage-specific chemically defined medium conditions. Induced SCPs (iSCPs) were further examined for their ability to differentiate into SCs. The identification and functionality of iSCPs and iSCP-differentiated SCs (iSCs) were confirmed according to morphology, lineage-specific markers, neurotropic factor secretion, and/or standard functional assays. Results Highly pure, Sox 10-positive of iSCPs (more than 95% purity) were generated from human skin fibroblasts within 3 weeks. Established iSCPs could be propagated in vitro while maintaining their SCP identity. Within 1 week, iSCPs could efficiently differentiate into SCs (more than 95% purity). The iSCs were capable of secreting various neurotrophic factors such as GDNF, NGF, BDNF, and NT-3. The in vitro myelinogenic potential of iSCs was assessed by myelinating cocultures using mouse dorsal root ganglion (DRG) neurons or human induced pluripotent stem cell (iPSC)-derived sensory neurons (HSNs). Furthermore, iSC transplantation promoted sciatic nerve repair and improved behavioral recovery in a mouse model of sciatic nerve crush injury in vivo. Conclusions We report a robust method for the generation of human iSCPs/iSCs that might serve as a promising cellular source for various regenerative biomedical research and applications, such as cell therapy and drug discovery, especially for the treatment of PNS injury and disorders.