Neural Cell News Volume 12.33 | Aug 22 2018

TOP STORY

SIRT6 Deficiency Results in Developmental Retardation in Cynomolgus Monkeys

Scientists generated a SIRT6-null cynomolgus monkey model using a CRISPR-Cas9-based approach. SIRT6 loss delays neuronal differentiation by transcriptionally activating the long non-coding RNA H19, and researchers were able to recapitulate this process in a human neural progenitor cell differentiation system. [Nature] Abstract | Editorial

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Genetically Engineered Human Cortical Spheroid Models of Tuberous Sclerosis

To determine the developmental origin of tuber cells, the authors established human cellular models of tuberous sclerosis complex by CRISPR-Cas9-mediated gene editing of tuberous sclerosis complex 1 (TSC1) or TSC2 in human pluripotent stem cells. [Nat Med] Abstract

Modeling Sporadic ALS in iPSC-Derived Motor Neurons Identifies a Potential Therapeutic Agent

Using induced pluripotent stem cell (iPSC) technology to generate stem and differentiated cells retaining the patients’ full genetic information, researchers established a large number of in vitro cellular models of sporadic ALS. These models showed phenotypic differences in their pattern of neuronal degeneration, types of abnormal protein aggregates, cell death mechanisms, and onset and progression of these phenotypes in vitro among cases. [Nat Med] Abstract

Selective Gene Dependencies in MYCN-Amplified Neuroblastoma Include the Core Transcriptional Regulatory Circuitry

Using unbiased genome-scale CRISPR-Cas9 approaches to detect genes involved in tumor cell growth and survival, the authors identified 147 candidate gene dependencies selective for MYCN-amplified neuroblastoma cell lines, compared to over 300 other human cancer cell lines. [Nat Genet] Abstract

Rapid and Efficient Induction of Functional Astrocytes from Human Pluripotent Stem Cells

Researchers demonstrated that overexpression of the transcription factors SOX9 and NFIB in human pluripotent stem cells rapidly and efficiently yields homogeneous populations of induced astrocytes. [Nat Methods] Abstract | Press Release

Sodium Valproate Rescues Expression of TRANK1 in iPSC-Derived Neural Cells that Carry a Genetic Variant Associated with Serious Mental Illness

Scientists used human-induced pluripotent stem cells (iPSC) and their neural derivatives to characterize common variants on chromosome 3p22 that have been associated by genome-wide association studies with major mental illnesses. [Mol Psychiatry] Abstract

Lgl1 Controls NG2 Endocytic Pathway to Regulate Oligodendrocyte Differentiation and Asymmetric Cell Division and Gliomagenesis

Investigators report that expression of the mouse homolog of Drosophila tumor suppressor lethal giant larvae 1 (Lgl1) is induced during oligodendrocyte (OL) differentiation. Lgl1 conditional knockout oligodendrocyte progenitor cells progeny retained NG2 and showed reduced OL differentiation, while undergoing more symmetric self-renewing divisions at the expense of asymmetric divisions. [Nat Commun] Full Article

3D Printed Stem‐Cell Derived Neural Progenitors Generate Spinal Cord Scaffolds

Successful bioprinting of oligodendrocyte progenitor cells in combination with spinal neuronal progenitor cells demonstrated a multicellular neural tissue engineering approach, where the ability to direct the patterning and combination of transplanted neuronal and glial cells can be beneficial in rebuilding functional axonal connections across areas of central nervous system tissue damage. [Adv Funct Mater] Abstract

Involvement of Advillin in Somatosensory Neuron Subtype-Specific Axon Regeneration and Neuropathic Pain

The authors revealed advillin expression restricted to isolectin B4-positive (IB4⁺) neurons in the adult dorsal root ganglia (DRG). Advillin knockout specifically impaired axonal regeneration in adult IB4⁺ DRG neurons. [Proc Natl Acad Sci USA] Full Article

Regulation of Protective Autophagy in Anoikis-Resistant Glioma Stem Cells by SDCBP/MDA-9/Syntenin

In nonadherent conditions, glioma stem cells displayed protective autophagy and anoikis-resistance, which correlated with expression of SDCBP/MDA-9/Syntenin. When SDCBP/MDA-9/Syntenin was absent, this protective mechanism was deregulated, leading to highly elevated and sustained levels of autophagy and consequently decreased cell survival. [Autophagy] Abstract

O-GlcNAc Signaling Orchestrates the Regenerative Response to Neuronal Injury in Caenorhabditis elegans

Performing in vivo laser axotomies in C. elegans, investigators found that neuronal regeneration is substantially increased by disruptions of either the O-linked β-N-acetylglucosamine (O-GlcNAc) transferase or the O-GlcNAcase that decrease and increase O-GlcNAc levels, respectively. [Cell Rep] Full Article | Graphical Abstract

Living Neurons with Tau Filaments Aberrantly Expose Phosphatidylserine and Are Phagocytosed by Microglia

Scientists report that living neurons with tau inclusions from P301S-tau mice exposed abnormally high amounts of phosphatidylserine because of the production of reactive oxygen species. Consequently, co-cultured phagocytes identified and phagocytosed the living neurons, thereby engulfing insoluble tau inclusions. [Cell Rep] Full Article | Graphical Abstract

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C9orf72-Mediated ALS and FTD: Multiple Pathways to Disease

The authors review the pathological and mechanistic features of C9orf72-associated frontotemporal dementia (FTD) and ALS, the model systems used to study these conditions, and the probable initiators of downstream disease mechanisms. [Nat Rev Neurol] Abstract

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A New Research Partnership to Find Treatments for Neurological Disorders

BioMotiv and Cure Network Dolby Acceleration Partners have entered into an agreement to develop small molecules that could provide new treatment options for patients with neurological disorders, such as Dravet syndrome, other epilepsies, and Alzheimer’s disease. [BioMotiv] Press Release

£1.5M Boost for Brain Tumor Research

Cancer experts at Edinburgh have received £1.5 million for research to better understand brain tumors. [University of Edinburgh] Press Release

AIVITA Biomedical Announces Initiation of First Clinical Site for ROOT OF CANCER Glioblastoma Trial

AIVITA Biomedical announced the initiation of its first clinical site for the company’s ROOT OF CANCER Phase II trial in patients with newly diagnosed glioblastoma. [AIVITA Biomedical] Press Release

ProMIS Neurosciences Oligomer Selective Antibody Therapeutic for Alzheimer’s Disease, PMN310, Shows Potential for Improved Safety Profile in Direct Comparison to Other Amyloid Beta-Directed Antibodies in Clinical Development

ProMIS Neurosciences, Inc. announced that its lead antibody candidate for Alzheimer’s disease (AD), PMN310, showed no binding to amyloid beta (Aβ) plaque in AD brain samples in stark contrast to BAN2401 and aducanumab which both displayed robust Aβ plaque reactivity. [ProMIS Neurosciences, Inc.] Press Release

Y-mAbs Receives Breakthrough Therapy Designation for Naxitamab for the Treatment of High Risk Neuroblastoma

Y-mAbs Therapeutics, Inc. announced that the company has received a Breakthrough Therapy designation for naxitamab, in combination with GM-CSF, for the treatment of high risk neuroblastoma refractory to initial therapy or with incomplete response to salvage therapy in patients older than 12 months of age with persistent, refractory disease limited to bone marrow with or without evidence of concurrent bone involvement. [Y-mAbs Therapeutics, Inc.] Press Release

AC Immune Announces Important Clinical Milestones for ACI-24 Vaccine in Alzheimer’s Disease and Down Syndrome

AC Immune SA announced two clinical milestone events related to ACI-24, its anti-Abeta vaccine against Alzheimer’s disease and Abeta-related cognitive decline in Down syndrome. [AC Immune SA] Press Release

In Defiance of Trump’s Budget, Senate Poised to Boost NIH Funding—Again

Ignoring President Donald Trump’s proposed budget, the Senate is setting up to approve a $2 billion boost in funding for the National Institutes of Health (NIH). [Fierce Biotech] Editorial

Hundreds of Chimps at the NIH Await Retirement. This Senator Wants to Help

Sen. Bill Cassidy is trying to help hundreds of chimpanzees enjoy an easy retirement in his home state of Louisiana. The Republican is pushing for an amendment to a major appropriations bill winding its way through Congress that would force the National Institutes of Health (NIH) to make good on a 2015 promise to move all its chimps out of research facilities. [STAT News] Editorial

Chief of Europe’s €1-Billion Brain Project Steps Down

The executive director of the European Union’s ambitious — but contentious — Human Brain Project has left his post after a disagreement with the institution that coordinates the initiative. [Nature News] Editorial

NEW Epigenetics in the Nervous System: Development and Disease
October 1-3, 2018
Stockholm, Sweden

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NEW Tenure Eligible Investigator – Neurobiology (Universite Bourgogne Franche-Comté)

Postdoctoral Position – Stem Cell-Based Modeling of Psychiatric Disease (Universitat Bonn)

Postdoctoral Position – Bioinformatic Analysis of Neural Development in Nematostella (University of Bergen)

Excellence in Science PhD Scholarship Award – Neuroscience (University of Technology Sydney)

Postdoctoral Research Scientist/Fellow – Neural Development and Neurodegenerative Diseases (Columbia University)

Postdoctoral Position – Molecular Mechanisms & Neural Circuits of Memory & Behavior (Rutgers University)

Senior/Principal Fellow or Professor – Program Leader for Animal Models (UK Dementia Research Institute)

Scientist/Assistant Professor – Neuroscience (The Hospital for Sick Children)

Postdoctoral Associate – Cerebral Organoids (Weill Cornell Medicine)

Postdoctoral Associate – hiPSC-Based Brain Organoids (Rutgers University)

Multiple Faculty Positions – Neuroscience and Neuroengineering (Tsinghua University)

Faculty Members – Neuroscience (Mercer University)

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