Neural Cell News Volume 11.08 | Mar 1 2017

TOP STORY

EZH2 Is a Potential Therapeutic Target for H3K27M-Mutant Pediatric Gliomas

Researchers used a mouse model of diffuse intrinsic pontine glioma (DIPG) in which lysine 27 is substituted with methionine (H3K27M) potentiates tumorigenesis. Using this model and primary patient-derived DIPG cell lines, they showed that H3K27M-expressing tumors require polycomb repressive complex 2 for proliferation. They demonstrated that small-molecule EZH2 inhibitors abolish tumor cell growth through a mechanism that is dependent on the induction of the tumor-suppressor protein p16^INK4A. [Nat Med] Abstract | Press Release

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Hallmarks of Alzheimer’s Disease in Stem-Cell-Derived Human Neurons Transplanted into Mouse Brain

Scientists transplanted human pluripotent stem cells-derived cortical neuronal precursors into the brain of a murine Alzheimer’s disease (AD) model. Human neurons differentiated and integrated into the brain, expressed 3R/4R Tau splice forms, showed abnormal phosphorylation and conformational Tau changes, and underwent neurodegeneration. Cell death was dissociated from tangle formation in this natural 3D model of AD. [Neuron] Abstract | Press Release

Synaptic Vesicle Glycoprotein 2C (SV2C) Modulates Dopamine Release and Is Disrupted in Parkinson Disease

Investigators identified SV2C as a mediator of dopamine homeostasis and report that disrupted expression of SV2C within the basal ganglia is a pathological feature of Parkinson disease. [Proc Natl Acad Sci USA] Abstract

An Hdac1/Rpd3-Poised Circuit Balances Continual Self-Renewal and Rapid Restriction of Developmental Potential during Asymmetric Stem Cell Division

Scientists demonstrated that the histone deacetylase Hdac1/Rpd3 functions together with self-renewal transcriptional repressors to maintain the earmuff immature intermediate neural progenitors enhancer in an inactive but poised state in neuroblasts. [Dev Cell] Abstract | Graphical Abstract

In Vitro Modeling of Blood-Brain Barrier with Human iPSC-Derived Endothelial Cells, Pericytes, Neurons, and Astrocytes via Notch Signaling

The authors generated an in vitro model of the blood-brain barrier by differentiating human induced pluripotent stem cells (hiPSCs) into all four populations. When the four hiPSC-derived populations were co-cultured, endothelial cells were endowed with features consistent with brain endothelial cells, including a high expression of nutrient transporters and efflux transporters, and strong barrier function based on tight junctions. [Stem Cell Reports] Full Article | Graphical Abstract

Direct Generation of Human Neuronal Cells from Adult Astrocytes by Small Molecules

Scientists report that human adult astrocytes could be converted into neuronal cells by a different set of small molecules. These induced cells exhibited typical neuronal morphologies, expressed neuronal markers, and displayed neuronal electrophysiological properties. Genome-wide RNA-sequencing analysis showed that the global gene expression profile of induced neuronal cells resembled that of human embryonic stem cell-differentiated neurons. [Stem Cell Reports] Full Article

RIPK3 Interactions with MLKL and CaMKII Mediate Oligodendrocytes Death in the Developing Brain

The authors aimed to explore the mechanisms of receptor-interacting proteins (RIP)-mediated oligodendrocytes death in the developing brain. Oligodendrocytes necroptosis was induced by oxygen-glucose deprivation plus caspase inhibitor zVAD treatment in vitro. [Cell Death Dis] Full Article

Inflammation-Induced miRNA-155 Inhibits Self-Renewal of Neural Stem Cells via Suppression of CCAAT/Enhancer Binding Protein β (C/EBPβ) Expression

Researchers hypothesized that miR-155 mediates inflammation-induced suppression of neural stem cell (NSC) self-renewal. Using primary mouse NSCs and human NSCs derived from induced pluripotent stem cells, they demonstrated that three important genes involved in NSC self-renewal are suppressed by miR-155. They also demonstrated that suppression of self-renewal genes is mediated by the common transcription factor C/EBPβ, which is a direct target of miR-155. [Sci Rep] Full Article

17β-Oestradiol Promotes Differentiation of Human Embryonic Stem Cells into Dopamine Neurons via Cross-Talk Between Insulin-Like Growth Factors-1 and Oestrogen Receptor β

Investigators studied the effects of E2 on dopamine neuron induction of human embryonic stem cells (hESCs) and its related signaling pathways using the three-stage protocol. E2 was applied to hESCs-derived human embryoid bodies and the effects of E2 on neural cells differentiation were investigated. [J Cell Mol Med] Full Article

Embryonic Stem Cell-Derived Neurons Grown on Multi-Electrode Arrays as a Novel In Vitro Bioassay for the Detection of Clostridium botulinum Neurotoxins

Scientists aimed to establish an in vitro assay as an alternative to the widely used in vivo mouse bioassay. They reported a novel C. botulinum neurotoxin detection assay using mouse embryonic stem cell-derived neurons cultured on multi-electrode arrays. [Front Pharmacol] Full Article | Press Release

Multidrug Resistance in Glioblastoma Stem-Like Cells: Role of the Hypoxic Microenvironment and Adenosine Signaling

The authors discuss chemoresistance in glioblastoma multiforme and the effect of the hypoxic microenvironment and adenosine on multiple drug resistance mechanisms. [Mol Aspects Med] Abstract

Visit our reviews page to see a complete list of reviews in the neural cell research field.

Tocagen Receives Breakthrough Therapy Designation from U.S. Food and Drug Administration for Toca 511 & Toca FC in Recurrent High Grade Glioma

Tocagen Inc., announced the U.S. Food and Drug Administration has granted Toca 511 & Toca FC Breakthrough Therapy Designation for the treatment of patients with recurrent high grade glioma. [Tocagen Inc.] Press Release

Initial Results Positive for CelGro^® in Human Nerve Regeneration

Orthocell announced positive initial safety and tolerability results for its CelGro^® collagen-based medical device in a clinical study examining its use to augment the repair of nerve damage. [Orthocell (Business Wire, Inc.)] Press Release

Neurotrope Bioscience Concludes Patient Dosing and Monitoring in its 148 Patient Phase II Clinical Trial of Moderate to Severe Alzheimer’s Dementia

Neurotrope, Inc. announced the conclusion of dosing and patient monitoring in its Phase II double blind, placebo controlled clinical trial of bryostatin-1 in the treatment of moderate to severe Alzheimer’s dementia. [Neurotrope, Inc.] Press Release

Georgetown Announces Phase II Clinical Trial of Nilotinib for Parkinson’s Disease

Georgetown University Medical Center announced the launch of a Phase II clinical trial to study the safety of the cancer drug nilotinib and its effects on clinical outcomes and biomarkers in people with Parkinson’s disease. [Georgetown University Medical Center] Press Release

Accera Announces Results of Its First Phase III Study in Mild-To-Moderate Alzheimer’s Disease

Accera, Inc., announced results of the AC-1204 Phase III study for the treatment of mild-to-moderate Alzheimer’s disease. Patients treated with AC-1204 did not demonstrate a statistically significant difference at 26 weeks compared with patients treated with placebo, as measured by the Alzheimer’s disease Assessment Scale-Cognitive Subscale test. [Accera, Inc.] Press Release

Peer-Review Activists Push Psychology Journals towards Open Data

An editor on the board of a journal published by the prestigious American Psychological Association has been asked to resign in a controversy over data sharing in peer review. Gert Storms — who says he won’t step down — is one of a few hundred scientists who have vowed that, from the start of this year, they will begin rejecting papers if authors won’t publicly share the underlying data, or explain why they can’t. [Nature News] Editorial

Senior Republican Lawmaker Has Some Advice for U.S. Science Marchers

The chairman of a congressional spending panel that oversees a wide swath of U.S. science agencies has some unusual advice for scientists planning to march on 22 April: Don’t talk about research. Instead, demand that Congress find a way to cut mandatory spending programs. [ScienceInsider] Editorial

Trump’s 2018 Budget Will Squeeze Civilian Science Agencies

The chunk of the federal budget that includes most of the U.S. government’s spending on basic science would shrink by 10.5% in 2018 under a plan outlined by President Donald Trump and administration officials. [ScienceInsider] Editorial

Departing Senior NSF Manager Offers Hopeful Assessment of Agency’s Future

The top aide to National Science Foundation (NSF) Director France Córdova has returned to his university after failing to win confirmation as deputy NSF director. But engineer Richard Buckius says his departure, less than a week after President Donald Trump took office, was long in the cards and not a political statement. In fact, Buckius predicts that NSF and academic research will do fine under the new Trump administration. [ScienceInsider] Editorial

UK Scientists Welcome Changes to Controversial Research Reforms

Amendments aim to protect autonomy and the independence of research funders from political interference. [Nature News] Editorial

NEW 2^nd Global Cancer Summit 2017
March 22-24, 2017
Kuala Lumpur, Malaysia

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Research Associate – Alzheimer’s Disease (King’s College London)

Postdoctoral Studies – In Vitro Neural Systems (Karolinska Institute)

PhD Student – Developmental Neuroscience (Karolinska Institute)

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

Assistant Professor – Neuroscience (Pennsylvania State University)

Postdoctoral Fellow – Translational Neuroscience and Neuroregeneration (Houston Methodist Research Institute)

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)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

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