Neural Cell News 11.43 November 1, 2017 | |
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TOP STORYMaintenance of Neural Progenitor Cell Stemness in 3D Hydrogels Requires Matrix Remodeling Neural progenitor cell culture within 3D hydrogels is an attractive strategy for expanding a therapeutically relevant number of stem cells. The authors identified matrix remodeling, in the absence of cytoskeletal tension generation, as a previously unknown strategy to maintain stemness in 3D. [Nat Med] Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)Scientists describe a somatic mouse model wherein histone (H)3.3K27M and Trp53 loss alone are sufficient for neoplastic transformation if introduced in utero. H3.3K27M-driven lesions are clonal, H3K27me3 depleted, Olig2 positive, highly proliferative, and diffusely spreading, thus recapitulating hallmark molecular and histopathological features of pediatric high-grade gliomas. [Cancer Cell] Abstract | Graphical Abstract Researchers showed that pleckstrin homology containing family member 5 (Plekhg5) modulates autophagy of synaptic vesicles in axon terminals of motoneurons via its function as a guanine exchange factor for Rab26, a small GTPase that specifically directs synaptic vesicles to preautophagosomal structures. [Nat Commun] Full Article A Neuroprotective Astrocyte State Is Induced by Neuronal Signal EphB1 but Fails in ALS Models Investigators showed that ephrin type-B receptor 1 (EphB1) is upregulated in injured motor neurons, which in turn can activate astrocytes through ephrin-B1-mediated stimulation of signal transducer and activator of transcription-3. [Nat Commun] Full Article Low-grade astrocytomas (LGAs) carry neomorphic mutations in isocitrate dehydrogenase (IDH) concurrently with P53 and ATRX loss. To model LGA formation, researchers introduced R132H IDH1, P53 shRNA, and ATRX shRNA into human neural stem cells. These oncogenic hits blocked NSC differentiation, increased invasiveness in vivo, and led to a DNA methylation and transcriptional profile resembling IDH1 mutant human LGAs. [Cell Rep] Full Article | Graphical Abstract The authors found that developmental transcriptome analysis of default-differentiated human pluripotent stem cells (hPSNs) revealed a gene expression program resembling in vivo CGE/LGE subpallial domains and GABAergic signaling. A combination of bioinformatic, functional, and immunocytochemical analysis further revealed that hPSNs consist of both cortical glutamatergic and CGE-like GABAergic neurons. [Stem Cell Reports] Full Article Generation of a Motor Nerve Organoid with Human Stem Cell-Derived Neurons Understanding of the axonal fascicle has been hampered by lack of an in vitro model system. Investigators report the generation of a nerve organoid composed of a robust fascicle of axons extended from a spheroid of human stem cell-derived motor neurons within a custom-designed microdevice. [Stem Cell Reports] Full Article As mitochondria play a major role in the rapid buffering of cytosolic calcium, researchers hypothesized that altered mitochondrial calcium handling contributes to dendritic retraction elicited by the leucine-rich repeat kinase 2 (LRRK2)-G2019S and -R1441C mutations. In primary mouse cortical neurons or patient fibroblasts expressing mutant LRRK2, they observed increased depolarization-induced mitochondrial calcium uptake. [J Neurosci] Abstract The authors showed that Zika virus (ZIKV) infects the subventricular zone in human fetal brain tissues and that the tissue tropism broadens with the progression of gestation. Their research demonstrated also that intermediate progenitor cells are the main target cells for ZIKV. Post-mitotic committed neurons become susceptible to ZIKV infection as well at later stages of gestation. [Sci Rep] Full Article On-Demand Optogenetic Activation of Human Stem-Cell-Derived Neurons Investigators report a simple but precise Cre-loxP-based strategy for generating conditional, and thereby stable, optogenetic human stem-cell lines. These cells can be easily and efficiently differentiated into functional neurons, and optogene expression can be triggered by administering Cre protein to the cultures. [Sci Rep] Full Article | |
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REVIEWSModeling Neurological Diseases Using iPSC-Derived Neural Cells The authors discuss how induced pluripotent stem cells (iPSC)-derived neural cells provide valuable tools for studying neurological disease mechanisms, developing potential therapies, and deepening our understanding of the nervous system. [Cell Tissue Res] Abstract Visit our reviews page to see a complete list of reviews in the neural cell research field. | |
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SCIENCE NEWSTocagen Inc. reported updated data demonstrating long-term durable responses, and the conversion of initial partial responses into complete responses, from a Phase I study of Tocagen’s investigational product, Toca 511 & Toca FC, for the treatment of patients with recurrent high-grade glioma, a type of brain tumor. [Press release from Tocagen Inc. discussing research presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, Philadelphia] Press Release Probiodrug to Present Data from Its Phase IIa SAPHIR Study Probiodrug AG announced that it will present data of the Phase IIa SAPHIR Study. [Press release from Probiodrug AG discussing research presented at the Clinical Trials on Alzheimer’s Disease (CTAD) 2017, Boston] Press Release | |
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INDUSTRY NEWSCerveau Technologies, Inc. Announces a Partnership with Landmark Alzheimer’s Disease DIAN-TU Trial Cerveau Technologies, Inc. announced a research collaboration involving use of its investigational imaging agent (MK-6240) by the international team led by the Dominantly Inherited Alzheimer’s Network Trial Unit (DIAN-TU) at Washington University School of Medicine in St. Louis in a worldwide clinical trial aimed at finding treatments to prevent Alzheimer’s disease. [Cerveau Technologies, Inc. (Business Wire, Inc.)] Press Release Biogen and Ionis Win Prestigious Prix Galien Award for SPINRAZA as Best Biotechnology Product Biogen and Ionis have been awarded the prestigious 2017 Prix Galien USA Award for Best Biotechnology Product for SPINRAZA®. [Biogen Inc.] Press Release Biohaven Pharmaceuticals, Inc. announced that the U.S. FDA has notified the company that it may proceed with its clinical investigation of sublingual BHV-0223 as a potential treatment for patients with ALS. [Biohaven Pharmaceuticals, Inc.] Press Release Transgene announced that the first patient with recurrent glioblastoma has been treated in the first-in-human clinical trial (Oncovirac trial) of TG6002, a novel oncolytic virus. [Transgene] Press Release Inovio Pharmaceuticals, Inc. initiated a Phase Ib/IIa immuno-oncology trial in patients with newly diagnosed glioblastoma designed to evaluate cemiplimab, a PD-1 inhibitor developed by Regeneron Pharmaceuticals, Inc., in combination with Inovio’s INO-5401 T cell activating immunotherapy encoding multiple antigens and INO-9012, an immune activator encoding IL-12. [Inovio Pharmaceuticals, Inc.] Press Release Voyager Therapeutics Announces Update to Parkinson’s Disease Program Voyager Therapeutics, Inc. announced an update to its VY-AADC program for advanced Parkinson’s disease. Under Voyager’s Collaboration Agreement with Sanofi Genzyme, Sanofi Genzyme had an exclusive option for ex-U.S. development and commercial rights to VY-AADC. Based on Voyager’s understanding that because this option did not include rights in the U.S., Sanofi Genzyme informed Voyager that it has decided not to exercise its rights to this program. [Voyager Therapeutics, Inc.] Press Release | |
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POLICY NEWSPlans to Promote German Research Excellence Come under Fire Observers questioned whether the 88 selected projects for the The Excellence Initiative represent Germany’s best science, particularly because the focus for selection has shifted away from basic science and towards applied research. [Nature News] Editorial Six Papers by Disgraced Surgeon Should Be Retracted, Report Concludes Sweden’s national scientific ethics board, the Expert Group on Misconduct in Research, has concluded that six papers authored by disgraced surgeon Paolo Macchiarini should be retracted. The papers describe the purported clinical success of artificial trachea “seeded” with a patient’s own stem cells. All three patients described in the papers died of complications related to the implant. [ScienceInsider] Editorial Spanish Government Takes Control of Catalonian Universities The Spanish government has taken over responsibility for higher education and research in Catalonia, following the region’s unilateral declaration of independence. It will retain control of spending on research centres and universities, which the League of European Research Universities says threatens institutional autonomy. [Nature News] Editorial
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EVENTSNEW 25th Annual Conference of The American Society for Neural Therapy and Repair Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Associate Professor – Neurology (Massachusetts General Hospital & Harvard Medical School) Assistant Professor – Cellular and Molecular Neuroscience (University of British Columbia) Faculty Position – Spinal Cord and Brain Injury Research (Indiana University) PhD Student – Brain Organoids (University of Antwerp) PhD Students – Glioblastomas (Various Organizations) PhD Position – Extracellular Vesicles in Neural Cell Communication (Institut of Molecular Biology) PhD Studentships – Molecular Biology (Medical Research Council, Laboratory of Molecular Biology) Faculty Position – Neurobiology (University of California, Berkeley) Faculty Members – Neuroscience (Mercer University) Postdoctoral Researcher – Stem Cell Differentiation (University of Oklahoma) Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.
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