Neural Cell News Volume 11.12 | Mar 29 2017

TOP STORY

m⁶A Demethylase ALKBH5 Maintains Tumorigenicity of Glioblastoma Stem-Like Cells by Sustaining FOXM1 Expression and Cell Proliferation Program

The dynamic and reversible N⁶-methyladenosine (m⁶A) RNA modification installed and erased by N⁶:-methyltransferases and demethylases regulates gene expression and cell fate. Researchers showed that the m⁶A demethylase ALKBH5 is highly expressed in glioblastoma stem-like cells (GSCs). Silencing ALKBH5 suppressed the proliferation of patient-derived GSCs. [Cancer Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Purine Synthesis Promotes Maintenance of Brain Tumor Initiating Cells in Glioma

Scientists linked metabolic dysregulation in human brain tumor initiating cells (BTICs) to a nexus between MYC and de novo purine synthesis, mediating glucose-sustained anabolic metabolism. Inhibiting purine synthesis abrogated BTIC growth, self-renewal and in vivo tumor formation by depleting intracellular pools of purine nucleotides, supporting purine synthesis as a potential therapeutic point of fragility. [Nat Neurosci] Abstract

Reducing Expression of Synapse-Restricting Protein Ephexin5 Ameliorates Alzheimer’s-Like Impairment in Mice

The authors reported that amyloid-β (Aβ) is sufficient to acutely promote the production of Ephexin5 in mature hippocampal neurons and in mice expressing human amyloid precursor protein, a model for familial Alzheimer’s disease (AD) that produces high brain levels of Aβ. Ephexin5 expression was highly elevated in the hippocampi of human AD patients, indicating its potential relevance to AD. [J Clin Invest] Full Article | Press Release

The Super Elongation Complex Drives Neural Stem Cell Fate Commitment

Scientists used Drosophila neuroblasts to demonstrate that the super elongation complex (SEC) acts as an intrinsic amplifier to drive cell fate commitment. SEC is highly expressed in neuroblasts, where it promotes self-renewal by physically associating with Notch transcription activation complex and enhancing hairy and E(spl) (HES) transcription. HES in turn upregulates SEC activity, forming an unexpected self-reinforcing feedback loop with SEC. [Dev Cell] Abstract | Graphical Abstract

Single-Cell RNA-Seq Reveals Hypothalamic Cell Diversity

Investigators reported single-cell RNA sequencing results of adult mouse hypothalamus, which defines 11 non-neuronal and 34 neuronal cell clusters with distinct transcriptional signatures. Analyses of cell-type-specific transcriptomes revealed gene expression dynamics underlying oligodendrocyte differentiation and tanycyte subtypes. [Cell Rep] Full Article | Graphical Abstract

Intrastriatal Transplantation of Human Neural Stem Cells Restores the Impaired Subventricular Zone in Parkinsonian Mice

To gain new insights into the mechanisms of 6-hydroxydopamine (6-OHDA)-induced lesioning and therapeutic efficacy of human neural stem cells (hNSCs) transplantation, the striatum of intrastriatal 6-OHDA-injected Parkinsonian mice were unilaterally engrafted with undifferentiated hNSCs. [Stem Cells] Abstract

Inhibition of Autophagy Prevents Irradiation-Induced Neural Stem and Progenitor Cell Death in the Juvenile Mouse Brain

Scientists evaluated the effect of autophagy inhibition on neural stem and progenitor cell death in the juvenile brain. Cell death and proliferation as well as microglia activation and inflammation were evaluated in the dentate gyrus of the hippocampus and in the cerebellum after irradiation. [Cell Death Dis] Full Article

Aberrant iPSC-Derived Human Astrocytes in Alzheimer’s Disease

The authors reported the development of a human induced pluripotent stem cell (iPSC)-derived astrocyte model created from healthy individuals and patients with either early-onset familial Alzheimer’s disease (AD) or the late-onset sporadic form of AD. Their chemically defined and highly efficient model provided >95% homogeneous populations of human astrocytes within 30 days of differentiation from cortical neural progenitor cells. [Cell Death Dis] Full Article

Therapeutic Efficacy of Neural Stem Cells Originating from Umbilical Cord-Derived Mesenchymal Stem Cells in Diabetic Retinopathy

Scientists evaluated the effects of intravitreal injection of neural stem cells (NSCs) originating from human umbilical cord-derived mesenchymal stem cells (MSCs) on neurodegeneration of diabetic retinopathy (DR) in rats. NSCs originating from MSCs demonstrated a neuroprotective effect by increasing the number of surviving RGCs and significantly reducing the progression of DR. [Sci Rep] Full Article

Derivation of Functional Human Astrocytes from Cerebral Organoids

Investigators report a protocol to generate human functional astrocytes from cerebral organoids derived from human pluripotent stem cells. They found that organoid-derived astrocytes strongly supported neuronal survival and neurite outgrowth and responded to ATP through transient calcium wave elevations, which are hallmarks of astrocyte physiology. [Sci Rep] Full Article

β-Arrestin 1 Has an Essential Role in Neurokinin-1 Receptor-Mediated Glioblastoma Cell Proliferation and G2/M Phase Transition

Researchers showed that the ARRB1-mediated signaling pathway is essential for neurokinin-1 (NK1)-mediated glioblastoma cell proliferation. ARRB1 knockdown significantly inhibited NK1-mediated glioblastoma cell proliferation and induced G2/M phase cell-cycle arrest. ARRB1-knockdown cells showed remarkable downregulation of CDC25C/CDK1/cyclin B1 activity. [J Biol Chem] Abstract

Stem Cell Transplantation Therapy for Multifaceted Therapeutic Benefits after Stroke

Scientists discuss the characteristics of cell therapy in different ischemic models and the application of stem cells and progenitor cells as regenerative medicine for the treatment of stroke. [Prog Neurobiol] Abstract

Parkinson Disease

The authors discuss experimental therapies that have tried to restore striatal dopamine by gene-based and cell-based approaches. The aggregation and cellular transport of α-synuclein have become therapeutic targets. One of the greatest current challenges is to identify markers for prodromal disease stages, which would allow novel disease-modifying therapies to be started earlier. [Nat Rev Dis Primers] Abstract

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Aprea Therapeutics Announces Research Collaboration with Memorial Sloan Kettering Cancer Center

Aprea Therapeutics announced a collaboration with Memorial Sloan Kettering Cancer Center to study the effects of reactivation of tumor suppressor protein p53 by APR-246. The goal of the collaboration is to evaluate and characterize preclinical efficacy of APR-246 in combination with multiple other anti-cancer agents and across multiple tumor types. [Aprea Therapeutics] Press Release

FDA Approves Roche’s OCREVUS^™ (Ocrelizumab) for Relapsing and Primary Progressive Forms of Multiple Sclerosis

Roche announced that the US Food and Drug Administration (FDA) approved OCREVUS^™ as the first and only medicine for both relapsing and primary progressive forms of multiple sclerosis (MS). The majority of people with MS have a relapsing form or primary progressive MS at diagnosis. [Roche] Press Release

EUSA Pharma and Apeiron Biologics Receive Positive CHMP Opinion for Dinutuximab Beta for the Treatment of High-Risk Neuroblastoma in Europe

EUSA Pharma and Apeiron Biologics announced that the European Medicines Agency’s Committee for Medicinal Products for Human Use has adopted a positive opinion recommending the approval of dinutuximab beta for use in the treatment of high-risk neuroblastoma. [EUSA Pharma] Press Release

European Commission Considering Leap into Open-Access Publishing

One of Europe’s biggest science spenders could soon branch out into publishing. The European Commission, which spends more than €10 billion annually on research, may follow two other big league funders, the Wellcome Trust and the Bill & Melinda Gates Foundation, and set up a “publishing platform” for the scientists it funds, in an attempt to accelerate the transition to open-access publishing in Europe. [ScienceInsider] Editorial

Europe Says University of California Deserves Broad Patent for CRISPR

The European Patent Office announced its “intention to grant a patent” to the University of California (UC) for its broad-based claims about the genome-editing tool popularly known as CRISPR. UC, on behalf of several parties, has been in a pitched battle with the Broad Institute of Cambridge, Massachusetts, over CRISPR patents, and the new decision marks a sharp departure from the position of the U.S. Patent and Trademark Office. [ScienceInsider] Editorial

Playing No Trump at AAAS Policy Forum

The relationship between U.S. scientists and the Trump administration hit a new low after organizers of a major annual science policy conference were unable to find anyone willing to discuss the president’s priorities. [ScienceInsider] Editorial

NEW Neural Circuits in the Past, Present and Future
May 14-17, 2017
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West Palm Beach, Florida, United States

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NEW Associate/Full Professor – Regenerative Medicine (University Of Florida)

NEW Postdoctoral Fellow/Experienced Scientist – Stem Cells and Epigenetics (University of Michigan)

Assistant/Associate Professor – Canada Research Chair in Mental Health (University of Alberta)

Senior Scientist – Cognitive Neurophysiology (Forschungszentrum Jülich – FZJ – Helmholtz Association)

Postdoctoral Fellow – Stem Cell Dynamics in the Adult Hippocampus (The Francis Crick Institute)

Postdoctoral Research Associate – Developmental Neuroscience (University of Nebraska Medical Center)

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

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

Assistant Professor – Neuroscience (Pennsylvania State University)

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

Postdoctoral Researcher – Stem Cell Differentiation (University of Oklahoma)

Postdoctoral Positions – Stem Cell Technology/Neuroscience/Drug Discovery (University of California Davis)

Neuroscientist – Precision Neurotherapeutics (University of California Davis)

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