Neural Cell News Volume 11.09 | Mar 8 2017

TOP STORY

Spatiotemporal Genomic Architecture Informs Precision Oncology in Glioblastoma

The authors studied genomic and expression profiles across 127 multisector or longitudinal specimens from 52 individuals with glioblastoma. Using bulk and single-cell data, they found that samples from the same tumor mass share genomic and expression signatures, whereas geographically separated, multifocal tumors and/or long-term recurrent tumors are seeded from different clones. [Nat Genet] Abstract

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Differentiation of Human and Murine Induced Pluripotent Stem Cells to Microglia-Like Cells

Scientists report the differentiation of human induced pluripotent stem cells (iPSC) into microglia-like cells by exposure to defined factors and co-culture with astrocytes. These iPSC-derived microglia had the phenotype, gene expression profile and functional properties of brain-isolated microglia. [Nat Neurosci] Abstract

The Auxiliary Calcium Channel Subunit α2δ4 Is Required for Axonal Elaboration, Synaptic Transmission, and Wiring of Rod Photoreceptors

In the mammalian retina, rod photoreceptors form selective contacts with rod ON-bipolar cells by aligning the presynaptic voltage-gated Ca²⁺ channel directing glutamate release (Ca_V1.4) with postsynaptic mGluR6 receptors. The authors showed that this coordination requires an extracellular protein, α2δ4, which complexes with Ca_V1.4 and the rod synaptogenic mediator, ELFN1, for trans-synaptic alignment with mGluR6. [Neuron] Abstract

Coordinated Generation of Multiple Ocular-Like Cell Lineages and Fabrication of Functional Corneal Epithelial Cell Sheets from Human iPS Cells

Investigators describe a protocol for the generation of a functional and transplantable corneal epithelium derived from human induced pluripotent stem (iPS) cells. When this protocol is followed, a proportion of iPS cells spontaneously form circular colonies, each of which is composed of four concentric zones. [Nat Protoc] Abstract

Fail-Safe System against Potential Tumorigenicity after Transplantation of iPSC Derivatives

The authors examined the efficacy of the inducible caspase-9 (iCaspase9) gene as a fail-safe against undesired tumorigenic transformation of induced pluripotent stem cells (iPSCs)-derived somatic cells. They used a lentiviral vector to transduce iCaspase9 into two iPSC lines and assessed its efficacy in vitro and in vivo. [Stem Cell Reports] Full Article

Inhibition of L-Type Ca²⁺ Channels by TRPC1-STIM1 Complex Is Essential for the Protection of Dopaminergic Neurons

Loss of dopaminergic (DA) neurons leads to Parkinson’s disease, however, the mechanism(s) for the vulnerability of DA neurons is not fully understood. Scientists demonstrated that TRPC1 regulates the L-type Ca²⁺ channel that contributes to the rhythmic activity of adult DA neurons in the substantia nigra region. [J Neurosci] Abstract

Astrocyte Pathology in a Human Neural Stem Cell Model of Frontotemporal Dementia Caused by Mutant TAU Protein

Investigators utilized CRISPR/Cas9 genome editing in human induced pluripotent stem cell-derived neural progenitor cells to repair the frontotemporal dementia-associated N279K MAPT mutation. [Sci Rep] Full Article

Disruptions in Asymmetric Centrosome Inheritance and WDR62-Aurora Kinase B Interactions in Primary Microcephaly

Recessive mutations in WD repeat domain 62 (WDR62) cause microcephaly and a wide spectrum of severe brain malformations. Disruption of the mouse ortholog resulted in microcephaly underlain by reduced proliferation of neocortical progenitors during late neurogenesis, abnormalities in asymmetric centrosome inheritance leading to neuronal migration delays, and altered neuronal differentiation. [Sci Rep] Full Article

Heterodimers of Serotonin Receptor Subtypes 2 Are Driven by 5-HT_2C Protomers

Scientists report that 5-HT2 receptors can form homo and heterodimers when expressed alone or co-expressed in transfected cells. Co-immunoprecipitation and bioluminescence resonance energy transfer studies confirmed that 5-HT2C receptors interact with either 5-HT_2A or 5-HT_2B receptors. [J Biol Chem] Abstract | Full Article

Swelling-Induced Chloride Current in Glioblastoma Proliferation, Migration and Invasion

Researchers investigated the effects of I_Cl,swell on cell viability, proliferation and migration in the human glioblastoma cell lines, U251 and U87, using a combination of patch clamp electrophysiology, MTT, colony formation, wound healing assays and Western immunoblotting. [J Cell Physiol] Abstract

Dopamine D2 Receptor and β-Arrestin 2 Mediate Amyloid-β Elevation Induced by Anti-Parkinson’s Disease Drugs, Levodopa and Piribedil, in Neuronal Cells

Scientists present that both levodopa and piribedil enhance the generation of amyloid-β and the activity of γ-secretase in human neuronal cells and primary neurons isolated from Alzheimer’s disease mouse. This effect was reduced by either the antagonism or the knockdown of dopamine D₂ receptor. [PLoS One] Full Article

Neuronal Survival in the Brain: Neuron Type-Specific Mechanisms

The authors focus on how immature neurons survive during normal and impaired brain development, both in the embryonic/neonatal brain and in brain regions associated with adult neurogenesis, and emphasize neuron type-specific mechanisms that help to survive for various types of immature neurons. [Cell Death Dis] Full Article

Role of Neuroinflammation in Neurodegeneration: New Insights

It is now accepted that the immune privilege of the brain is not absolute, and that cells of the central nervous system are sensitive to both the inflammatory events occurring in the periphery and to the infiltration of peripheral immune cells. This is particularly relevant for the progression of Alzheimer’s disease, in which it has been demonstrated that patients are more vulnerable to infection-related cognitive changes. [Alzheimers Res Ther] Full Article

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EnGeneIC Receives FDA Orphan Drug Designation for Targeted EDV^™ Nanocells to Treat Glioblastoma Multiforme

EnGeneIC Ltd. announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to EGFR-targeted, doxorubicin-loaded EDV nanocells for the treatment of glioblastoma multiforme. [EnGeneIC Ltd.] Press Release

Phase II Clinical Trial for Treatment of Mild Alzheimer’s Disease

Neurim Pharmaceuticals Ltd. announced that they are seeking up to 500 U.S. patients with mild Alzheimer’s Disease for the start of a Phase II Clinical trial of a new drug treatment that has the potential to slow the progression of early-stage Alzheimer’s Disease. [Neurim Pharmaceuticals Ltd. (PR Newswire Association LLC.)] Press Release

Renown Pharma Announces Successful Results of Apomorphine Sub-Lingual Spray Pharmacokinetic Study to Treat “OFF” Episodes in Parkinson’s Patients

Renown Pharma Limited announced the results of a pharmacokinetic study intended to compare the plasma concentrations of Renown’s sub-lingual apomorphine spray against the currently approved formulation of injectable apomorphine used to treat motor fluctuations, or “OFF” episodes, in Parkinson’s disease patients. [Renown Pharma Limited (PR Newswire Association LLC.)] Press Release

ImmunoCellular Therapeutics Provides Update on ICT-107 Phase III Glioblastoma Trial and Announces Advances in Stem-to-T-Cell Research Program

ImmunoCellular announced successful completion of the first milestone for the company’s Stem-to-T-cell program, the sequencing of a selected T cell receptor (TCR) gene. When inserted into a blood stem cell, this TCR gene is expected to enhance patients’ immune systems to produce killer T cells programmed to attack tumors. [ImmunoCellular Therapeutics, Ltd.] Press Release

Patchy Progress on Fixing Global Gender Disparities in Science

Although women are publishing more studies, being cited more often, and securing more coveted first-author positions than they were in the mid-1990s, overall progress towards gender parity in science varies widely by country and field. This is according to a massive report released on 8^th March that is the first to examine such a broad swath of disciplines and regions of the world over time. [Nature News] Editorial

Open-Data Contest Unearths Scientific Gems — and Controversy

When a prestigious medical journal challenged scientists to analyze data from a pivotal blood-pressure study in search of new findings, hundreds of researchers around the world rushed to sign up. The contest, sponsored by the New England Journal of Medicine, offered scientists a rare opportunity to access detailed trial data that otherwise might have remained proprietary for another year — if not indefinitely. But the competition, whose winners were announced on 7^th March, also illustrates the tension between speeding access to data and protecting the interests of those who laboured to collect them. [Nature News] Editorial

NEW AACR Annual Meeting 2017
April 1-5, 2017
Washington, D.C., United States

NEW Stem Cells and Regenerative Medicine 2^nd International Congress
April 19-21, 2017
Mashhad, Iran

NEW The Biology of Regenerative Medicine
April 25-27, 2017
Hinxton, United Kingdom

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NEW PhD Student and Postdoctoral Positions – Molecular and Cellular Biology/Systems Biology/Neurobiology (University of Fribourg)

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Scientist – Retina and CNS Degenerative Disease (University Health Network)

Assistant Professor – Neuroscience (Pennsylvania State University)

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Research Scientist – Neurobiology of the Visual System (National Eye Institute – National Institutes of Health)

Postdoctoral Researcher – Stem Cell Differentiation (University of Oklahoma)

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