Neural Cell News 13.03 January 30, 2019 | |
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TOP STORYOnset of Differentiation Is Post-Transcriptionally Controlled in Adult Neural Stem Cells The generation of neurogenic progeny involved translational repression of a subset of mRNAs, including mRNAs that encode the stem cell identity factors SOX2 and PAX6, and components of the translation machinery, which are enriched in a pyrimidine-rich motif. The decrease of mTORC1 activity as stem cells exited the cell cycle selectively blocked translation of these transcripts. [Nature] Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)Efficacy and toxicity screening in induced pluripotent stem cell (iPSC)-derived astrocytes and neurons showed that allosteric activation of CYP46A1 lowered cholesteryl esters specifically in neurons and was well tolerated by astrocytes. [Cell Stem Cell] Full Article | Press Release | Graphical Abstract Differentiation and Maturation of Oligodendrocytes in Human Three-Dimensional Neural Cultures Investigators developed a new differentiation method of human induced pluripotent stem cells to generate 3D brain organoids that contain oligodendrocytes as well as neurons and astrocytes, called human oligodendrocyte spheroids. [Nat Neurosci] Abstract | Press Release FGL2 Promotes Tumor Progression in the CNS by Suppressing CD103+ Dendritic Cell Differentiation Researchers showed that fibrinogen-like protein 2 (FGL2) was highly expressed in glioma stem cells and primary glioblastoma (GBM) cells. FGL2 knockout in tumor cells did not affect tumor cell proliferation in vitro or tumor progression in immunodeficient mice but completely impaired GBM progression in immune-competent mice. [Nat Commun] Full Article | Press Release Synchronizing the expression of three microRNAs in a gene therapy approach displayed significant anticancer synergism, abrogated this epigenetic-mediated, multi-protein tumor survival mechanism and resulted in a five-fold increase in survival when combined with chemotherapy in murine glioblastoma models. [Nat Commun] Full Article | Press Releae Human neurons derived from patient iPSCs carrying mutated TDP-43 showed altered sortilin splicing and reduced levels of activity-dependent brain-derived neurotrophic factor (BDNF) secretion, which could be restored by correcting the mutation. [EMBO J] Abstract | Graphical Abstract Loss of primary cilia abolished the ability of Atoh1 to keep granule neuron progenitors in a proliferative state. Mechanistically, Atoh1 promoted ciliogenesis by transcriptionally regulating Cep131, which facilitates centriolar satellite clustering to the basal body. [Dev Cell] Abstract | Graphical Abstract Investigators expressed dCas9-p300 or dCas9-HDAC8 fusion proteins to mimic or block activity-induced histone acetylation locally at enhancers. Adding histone acetylation increased Fos transcription by prolonging burst duration and resulted in higher Fos protein levels and an elevation of resting membrane potential. [Cell Rep] Full Article | Graphical Abstract REST and Neural Gene Network Dysregulation in iPSC Models of Alzheimer’s Disease The induced pluripotent stem cell (iPSC)-derived neural cells from sporadic Alzheimer’s disease patients exhibited accelerated neural differentiation and reduced progenitor cell renewal. Moreover, a similar phenotype appeared in Alzheimer’s disease cells and cerebral organoids derived from apolipoprotein E4 iPSCs. [Cell Rep] Full Article | Press Release | Graphical Abstract Isolation and Characterization of Patient-Derived CNS Metastasis-Associated Stromal Cell Lines Four different patient-derived cell lines (PDCs) of stromal and one PDC of tumorigenic origin were generated from breast or lung CNS metastases. PDCs were analyzed by DNA/RNA sequencing, DNA methylation profiling, and immunophenotypic assays. [Oncogene] Full Article Scientists observed that neuropilin-1 (Nrp1) mRNA was upregulated in layer five pyramidal neurons in the motor cortex 14 days after spinal cord injury (SCI), when the pruning occurred. Nrp1 knockdown using adeno-associated virus vector encoding Nrp1 shRNA in the hindlimb motor area impaired the pruning of collaterals after SCI. [Cell Death Dis] Full Article Electrophysiological recordings of field postsynaptic potentials and Ca2+ measures in striatal brain slices and differentiated SH-SY5Y cells showed that co-application of α-synuclein and the neurotoxic pesticide rotenone induced Ca2+ dysregulation and alteration of both synaptic transmission and cell function. The presence of the mitochondrial NCX inhibitor CGP-37157 prevented these alterations. [Cell Death Dis] Full Article Subscribe to one of our other 19 science newsletters such as Cancer Stem Cell News & ESC & iPSC News. | |
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REVIEWSHow the Epigenome Integrates Information and Reshapes the Synapse Investigators explore how epigenetic mechanisms give rise to stable alterations in neuronal function by modifying synaptic structure and function, and highlight studies that demonstrate how manipulating epigenetic mechanisms may push the boundaries of memory. [Nat Rev Neurosci] Abstract Exosomes – Beyond Stem Cells for Restorative Therapy in Stroke and Neurological Injury The authors consider the opportunities for exosome-based approaches to therapeutic amplification of brain repair and improvement of recovery after stroke, traumatic brain injury and other diseases in which neurorestoration could be a viable treatment strategy. [Nat Rev Neurol] Abstract Visit our reviews page to see a complete list of reviews in the neural cell research field. | |
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INDUSTRY NEWSNeurocrine Biosciences, Inc. and Voyager Therapeutics, Inc. announced the formation of a strategic collaboration focused on the development and commercialization of Voyager’s gene therapy programs, VY-AADC for Parkinson’s disease and VY-FXN01 for Friedreich’s ataxia, as well as rights to two programs to be determined. [Neurocrine Biosciences, Inc.] Press Release Roche announced the decision to discontinue CREAD I and CREAD 2 Phase III studies of the investigational anti-beta-amyloid molecule crenezumab in people with early sporadic AD. [F. Hoffmann-La Roche Ltd] Press Release John Theurer Cancer Center at Hackensack Meridian Health Hackensack University Medical Center announced that it is leading enrollment worldwide for WIZARD 201G, a global Phase II study in glioblastoma. The trial, sponsored by Boston Biomedical, is evaluating DSP-7888, an investigational cancer vaccine, in combination with bevacizumab for recurrent disease. [Hackensack Meridian Health] Press Release First US Patient in Novel Stem Cell Trial for Stroke Disability Enrolled at UTHealth The trial, called PISCES III, is a Phase IIb, randomized, placebo-controlled, multicenter study enrolling a total of 110 eligible ischemic stroke patients, age 35 to 75, who are experiencing persistent disability 6 to 12 months post-stroke. [The University of Texas Health Science Center at Houston (UTHealth)] Press Release Ironwood Pharmaceuticals, Inc. announced the initiation of a Phase I study evaluating IW-6463 in healthy volunteers. IW-6463 is an orally administered central nervous system (CNS)-penetrant soluble guanylate cyclase (sGC) stimulator that is being developed for the treatment of serious and orphan CNS disorders. [Ironwood Pharmaceuticals, Inc.] Press Release Alzheimer’s Association Funds Two-Year Extension of the SPRINT MIND Study The Alzheimer’s Association has awarded more than $800,000 to support the SPRINT MIND 2.0 Study, which will further investigate the impact of intensive blood pressure treatment on reducing risk of dementia. The newly funded study will continue and extend follow up of the SPRINT MIND trial participants. [Alzheimer’s Association] Press Release | |
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POLICY NEWSUS Government Shutdown’s Effects on Science Ripple Overseas From canceled conferences to delayed publications, fallout of the shutdown spread beyond US borders, prompting concerns about long-term damage to international collaboration. [The Scientist] Editorial How Brexit Threatens Irish Science’s Cross-Border Collaboration Scientists in Northern Ireland and the Republic of Ireland are worried that Brexit will upset the island’s research ecosystem, which has benefited from peace and economic growth over the past 20 years. [Nature News] Editorial
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EVENTSNEW The 14th International Conference on Alzheimer’s & Parkinson’s Diseases (AD/PDTM 2019) Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Postdoctoral Scholar – Brain Tumor Biology (Lund University) NEW Faculty Positions – Developmental Neurosciences (Kent State University) Postdoctoral Position – Stem Cells & Neurodegeneration (Lund University) Assistant Member – Developmental Neurobiology (St. Jude Children’s Research Hospital) Research Assistant – Cellular Neuroscience (Cardiff University) Research Fellow – Neuroscience (University College London) Associate Professor/Assistant Professor – Neuroscience (Hong Kong Baptist University) PhD – Neuroscience (Institute for Neuroscience) 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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