Neural Cell News Volume 12.16 | Apr 25 2018

TOP STORY

Developmental and Oncogenic Programs in H3K27M Gliomas Dissected by Single-Cell RNA-Seq

Researchers found that gliomas with histone H3 lysine27-to-methionine mutations (H3K27M-glioma) primarily contain cells that resemble oligodendrocyte precursor cells (OPC-like), whereas more differentiated malignant cells are a minority. OPC-like cells exhibited greater proliferation and tumor-propagating potential than their more differentiated counterparts and were at least in part sustained by PDGFRA signaling. [Science] Abstract

(Ranked by impact factor of the journal)

Synaptic Transmission from Subplate Neurons Controls Radial Migration of Neocortical Neurons

The authors report that subplate neurons, one of the first neuron types born in the neocortex, manage the multipolar-to-bipolar transition of migrating neurons. By histochemical, imaging, and microarray analyses on the mouse embryonic cortex, they found that subplate neurons extend neurites toward the ventricular side of the subplate and form transient glutamatergic synapses on the multipolar neurons just below the subplate. [Science] Abstract | Press Release

A Glial Signature and Wnt7 Signaling Regulate Glioma-Vascular Interactions and Tumor Microenvironment

Investigators showed that Olig2⁺ oligodendrocyte precursor-like glioma cells invade by single-cell vessel co-option and preserve the blood-brain barrier (BBB). Conversely, Olig2-negative glioma cells formed dense perivascular collections and promoted angiogenesis and BBB breakdown, leading to innate immune cell activation. [Cancer Cell] Abstract

Super-Obese Patient-Derived iPSC Hypothalamic Neurons Exhibit Obesogenic Signatures and Hormone Responses

Scientists developed a method to reliably differentiate human induced pluripotent stem cells (iPSCs) into hypothalamic-like neurons (iHTNs) capable of secreting orexigenic and anorexigenic neuropeptides. Transcriptomic profiling revealed that, although iHTNs maintain a fetal identity, they respond appropriately to metabolic hormones ghrelin and leptin. [Cell Stem Cell] Full Article | Press Release | Editorial | Graphical Abstract

NF-κB Activity Initiates Human ESC-Derived Neural Progenitor Cell Differentiation by Inducing a Metabolic Maturation Program

Researchers applied gene expression studies and transcription factor-activated reporter lentiviruses during in vitro neural specification of human pluripotent stem cells. They showed that nuclear factor κB orchestrates a multi-faceted metabolic program necessary for the maturation of neural progenitor cells during neurogenesis. [Stem Cell Reports] Full Article

THC Exposure of Human iPSC Neurons Impacts Genes Associated with Neuropsychiatric Disorders

Investigators exposed neurons derived from human induced pluripotent stem cells iPSCs to Δ⁹-tetrahydrocannabinol (THC), and identified diagnosis-specific differences not detectable in vehicle-controls. [Transl Psychiatry] Full Article

Nitration of Microtubules Blocks Axonal Mitochondrial Transport in a Human Pluripotent Stem Cell Model of Parkinson’s Disease

With the use of a patient-derived stem cell model of Parkinson’s disease, allowing comparison of dopaminergic neurons harboring a mutation in the α-synuclein gene against isogenic, mutation-corrected controls, scientists describe a novel mechanism whereby NO, generated from SNCA-A53T mutant neurons exposed to Rot or PQ/MB, inhibits anterograde mitochondrial transport through nitration of α-tubulin. [FASEB J] Abstract

BAP1 Induces Cell Death via Interaction with 14-3-3 in Neuroblastoma

Investigators found that the reduced expression of BRCA1-associated protein 1 (BAP1) promotes the survival of neuroblastoma cells, and restoring the levels of BAP1 in these cells facilitated a delay in S and G2/M phase of the cell cycle, as well as cell apoptosis. [Cell Death Dis] Abstract

Brain and Spinal Cord Injury Repair by Implantation of Human Neural Progenitor Cells Seeded onto Polymer Scaffolds

Scientists investigated the reparative ability and therapeutic potentials of biological bridges composed of human fetal brain-derived neural progenitor cells seeded upon poly(glycolic acid)-based scaffold implanted into the infarction cavity of a neonatal hypoxic-ischemic brain injury or the hemisection cavity in an adult spinal cord injury. [Exp Mol Med] Full Article

FoxJ1 Regulates Spinal Cord Development and Is Required for the Maintenance of Spinal Cord Stem Cell Potential

Forkhead box protein J1 (FoxJ1) loss perturbed embryonic progenitor proliferation and cell fate determination, and resulted in formation of adult ependymal cells having impaired stem cell potential and an inability to respond to spinal cord injury in both male and female animals. [Exp Cell Res] Full Article

The Transcription Factor MEF2A Plays a Key Role in the Differentiation/Maturation of Rat Neural Stem Cells into Neurons

Investigators showed that although MEF2A is present in undifferentiated neural stem cells, following differentiation it is expressed at significantly higher levels in a subset of neuronal compared to non-neuronal cells. [Biochem Biophys Res Commun] Full Article

Zika Virus Propagation and Release in Human Fetal Astrocytes Can Be Suppressed by Neutral Sphingomyelinase-2 Inhibitor GW4869

The authors found that Zika virus (ZIKV) specifically infected glial fibrillary acidic protein- and S100B-positive primary human astrocytes derived from fetal brains. In contrast, neuron-specific class III β-tubulin-positive neurons in the astrocyte cultures and SOX2-positive neural progenitor cells derived from the fetal brains were less susceptible to ZIKV infection compared with astrocytes. [Cell Discov] Full Article

The Role of Adult Hippocampal Neurogenesis in Brain Health and Disease

The authors review a possible link between the physiological functions of adult-born neurons and their roles in pathological conditions. [Mol Psychiatry] Abstract

Pharmacological Approaches Promoting Stem Cell-Based Therapy following Ischemic Stroke Insults

Scientists summarized the limitations of ischemia-induced neurogenesis and stem-cell transplantation, as well as the potential proneuroregenerative effects of drugs that may enhance efficacy of cell-based therapies. Specifically, they discussed drugs that enhance proliferation, migration, differentiation, survival and function connectivity of newborn neurons, which may restore neurobehavioral function and improve outcomes in stroke patients. [Acta Pharmacol Sin] Full Article

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New Data from IONIS-HTT Rx Phase I/II Study Demonstrates Correlation between Reduction of Disease-Causing Protein and Improvement in Clinical Measures of Huntington’s Disease

Ionis Pharmaceuticals, Inc. presented top-line data from the Phase I/II study of IONIS-HTTRx in people with early stage Huntington’s disease. [Press release from Ionis Pharmaceuticals, Inc. discussing research presented at the 70^th American Academy of Neurology (AAN) Meeting , Los Angeles] Press Release

Boston Scientific Announces Positive Late-Breaking Data from the INTREPID Study

Boston Scientific Corporation announced one-year data from the INTREPID study, the first and only prospective, double-blind, randomized, sham-controlled, multi-center study of deep brain stimulation for advanced, levodopa-responsive Parkinson’s disease in the United States. [Press release from Boston Scientific Corporation discussing research presented at the 70^th American Academy of Neurology (AAN) Meeting , Los Angeles] Press Release

New Analyses from Pivotal Phase III Trials of Oral Ozanimod in Relapsing Multiple Sclerosis

Celgene Corporation announced additional Phase III data analyses evaluating the efficacy and safety of ozanimod, a novel, oral, selective sphingosine 1-phosphate 1 and 5 receptor modulator, versus interferon beta-1a in patients with relapsing multiple sclerosis. [Press release from Celgene Corporation discussing research to be presented at the 70^th American Academy of Neurology (AAN) Meeting , Los Angeles] Press Release

STEMCELL Technologies Announces $45 Million Government Funding for Advanced Manufacturing Facility

STEMCELL Technologies announced a $45 million joint funding agreement between the Governments of Canada and British Columbia to help the company build a state-of-the-art advanced manufacturing facility. The funding agreement will accelerate the Vancouver company’s rapidly scaling business of providing cutting-edge reagents and tools to support life science researchers around the world working in the cell therapy and regenerative medicine fields. [STEMCELL Technologies Inc.] Press Release

Biogen and Ionis Expand Strategic Collaboration to Develop Drug Candidates for a Broad Range of Neurological Diseases

Biogen and Ionis Pharmaceuticals announced that they have expanded their strategic collaboration through a new ten-year collaboration agreement to develop novel antisense drug candidates for a broad range of neurological diseases. [Biogen] Press Release

Immunotherapy Clinical Trial Reveals Brain Tumor Shrinkage, Continues with Phase III Study

Following successful Phase I clinical trials, the Toca regimen – a new immunotherapy for patients with recurrent brain cancer – has advanced to a Phase III study, which is currently underway. [Atlantic NeuroSurgical Specialists Brain Tumor Center (PR Newswire Association LLC.)] Press Release

San Diego Leaders, Researchers Announce Milestone Grant as Alzheimer’s Crisis Widens

A coalition of brain scientists and civic leaders, including Mayor Kevin Faulconer and county Supervisors Dianne Jacob and Kristin Gaspar, announced that the federal government has awarded a $1.3 million grant to Sanford Burnham Prebys Medical Discovery Institute to advance the local search for a cure. [Sanford Burnham Prebys Medical Discovery Institute] Press Release

NYU Winthrop’s Research Institute: Stem Cells Reengineered to Act Like Brain Neurons May Hold New Hope for Finding Treatments for Alzheimer’s

NYU Winthrop Hospital’s Research Institute announced that Allison B. Reiss, M.D., Head of the Inflammation Section, received a $10,000 surprise grant from the Alzheimer’s Disease Resource Center to further the very promising Alzheimer’s research that Reiss and her team of physicians and scientists are conducting. [NYU Winthrop’s Hospital] Press Release

U.K. Commits to EU Trial Rules Post-Brexit as CRUK Hails ‘Fantastic News’

The U.K. government said it will endeavor to keep pace with the European Union’s impending changes in clinical trial procedures, bringing some solace to those wondering how the two will stay aligned after Brexit starts in earnest next March. [Questex LLC.] Editorial

Rent Increase Hits Europe’s Drug Regulator Before Brexit Move

With less than a year to go before the European Medicines Agency must leave its London headquarters because of Brexit, the agency is facing an unexpected rent increase that could cut into its budget for approving new medicines and overseeing clinical trials. [Nature News] Editorial

Singapore Bets Big on Synthetic Biology

Singapore has set its sights on becoming a global powerhouse in synthetic biology. The government is pouring money into a new research program and is encouraging scientists to make synthetic microorganisms, or redesign natural ones, that can be used to produce food, electronics, medicine and energy. [Nature News] Editorial

Scientists’ Early Grant Success Fuels Further Funding

Young researchers who narrowly miss out on postdoctoral grant struggle to compete with those who just qualify. [Nature News] Editorial

NEW 10^th International Heinrich F. C. Behr-Symposium on Stem Cells and Cancer
September 16-19, 2018
Heidelberg, Germany

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NEW Postdoctoral Positions – RNA Biology and Neurodegenerative Disease (Johns Hopkins University)

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Postdoctoral Position – Bacterial Virulence Factors (University of California, Irvine)

Postdoctoral Fellow – Neural Control of Circulation (MD Anderson Cancer Center)

Postdoctoral Position – Cancer, Immunotherapy, and Fibrosis (University of Alabama at Birmingham)

Scientist – Molecular Neuroscience (Loyola University Chicago)

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Postdoctoral Position – Pain in Mouse Models of Spinal Cord Injury (Indiana University)

Postdoctoral Position – Spinal Cord Injury (Nanyang Technological University)

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Faculty Members – Neuroscience (Mercer University)

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