Neural Cell News Volume 14.00 | Jan 08 2020

TOP STORY

A Patient-Derived Glioblastoma Organoid Model and Biobank Recapitulates Inter- and Intratumoral Heterogeneity

Investigators report methods for generating and biobanking patient-derived glioblastoma organoids that recapitulated the histological features, cellular diversity, gene expression, and mutational profiles of their corresponding parental tumors. [Cell] Abstract | Graphical Abstract | Press Release

(Ranked by impact factor of the journal)

Outer Radial Glia-like Cancer Stem Cells Contribute to Heterogeneity of Glioblastoma

Scientists found that multiple glia-like cancer stem cells (GSCs) subtypes existed within a single tumor. Within these GSCs, they identified an invasive cell population similar to outer radial glia, a fetal cell type that expanded the stem cell niche in normal human cortex. [Cell Stem Cell] Abstract | Graphical Abstract

p120-Catenin-Dependent Collective Brain Infiltration by Glioma Cell Networks

Researchers showed that glioma cells infiltrated the brain collectively as multicellular networks. Contacts between moving glioma cells were adaptive epithelial-like or filamentous junctions stabilized by N-cadherin, β-catenin and p120-catenin. [Nat Cell Biol] Abstract

Glucocerebrosidase Activity Modulates Neuronal Susceptibility to Pathological α-Synuclein Insult

Investigators examined the relationship between glucocerebrosidase activity and both pathogenic and non-pathogenic forms of α-synuclein in primary hippocampal, cortical, and midbrain neuron and astrocyte cultures, as well as in transgenic mice and a non-transgenic mouse model of Parkinson’s disease. [Neuron] Abstract | Graphical Abstract

m⁶A mRNA Methylation is Essential for Oligodendrocyte Maturation and CNS Myelination

The authors demonstrated that the oligodendrocyte lineage progression was accompanied by dynamic changes in N ⁶-methyladenosine modification on numerous transcripts. [Neuron] Abstract

TREM2 Regulates Microglial Cholesterol Metabolism upon Chronic Phagocytic Challenge

Researchers found that wild-type microglia acquired a disease-associated transcriptional state, while TREM2-deficient microglia remained largely homeostatic, leading to neuronal damage. [Neuron] Abstract | Graphical Abstract

Differential Regulation of Autophagy during Metabolic Stress in Astrocytes and Neurons

Scientists defined the molecular underpinnings of autophagy in primary cortical astrocytes in response to metabolic stress, and performed a comparative study in primary hippocampal neurons. [Autophagy] Abstract

Microglial IRF5-IRF4 Regulatory Axis Regulates Neuroinflammation after Cerebral Ischemia and Impacts Stroke Outcomes

Researchers genetically modified the interferon regulatory factor (IRF)5 and IRF4 signaling to explore their roles in stroke. Both in vitro and in vivo assays were utilized; IRF5 or IRF4 siRNA, lentivirus, and conditional knockout techniques were employed to modulate IRF5 or IRF4 expression in microglia. [Proc Natl Acad Sci USA] Abstract

Coupling of Terminal Differentiation Deficit with Neurodegenerative Pathology in Vps35-Deficient Pyramidal Neurons

The authors provided evidence that vacuolar protein sorting 35 (Vps35) in embryonic neurons was necessary for axonal and dendritic terminal differentiation. Loss of Vps35 in embryonic neurons resulted in not only terminal differentiation deficits, but also neurodegenerative pathology. [Cell Death Differ] Full Article

Identification of a Transient State during the Acquisition of Temozolomide Resistance in Glioblastoma

Investigators performed a longitudinal study, using a combination of mathematical models, RNA sequencing, single cell analyses, functional and drug assays in a human glioma cell line. [Cell Death Dis] Abstract

Off-Target Effect of the BMI1 Inhibitor PTC596 Drives Epithelial-esenchymal Transition in Glioblastoma Multiforme

Scientists report that when used at appropriate concentrations, pharmaceutical inhibitors of BMI1 could efficiently prevent glioblastoma multiforme colony growth and cancer stem cell self-renewal in vitro and significantly extend lifespan in terminally ill tumor-bearing mice. [npj Precis Oncol] Full Article

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The Future of Stem Cell Therapies for Parkinson Disease

The authors critically assess the potential translational and clinical research trajectory of cell-replacement therapies that comprise dopamine neurons derived from human pluripotent stem cells and address its possibilities and current limitations. [Nat Rev Neurosci] Abstract

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ATAI Life Sciences Partners with Neuronasal Inc. to Develop Novel Treatment for mild Traumatic Brain Injury (mTBI)

ATAI Life Sciences AG announced that it has partnered with Neuronasal Inc., to develop a short-term treatment for mild traumatic brain injury or concussion. [ATAI Life Sciences AG (PR Newswire, Inc.)] Press Release

ESCAPE Bio Announces Excellent Safety and Tolerability in Phase I Study of Oral S1P5 Receptor Agonist ESB1609

ESCAPE Bio, Inc., announced that ESB1609 demonstrated durable CSF pharmacokinetics and excellent safety and tolerability in a single ascending dose Phase I Study. ESB1609 is a novel, orally administered, brain-penetrant and highly-selective sphingosine 1-phosphate 5 receptor agonist. [ESCAPE Bio, Inc.] Press Release

Mount Sinai Receives More than $10 Million in Grant Funding for Brain Tumor Research

The Department of Neurosurgery at the Icahn School of Medicine at Mount Sinai has received more than $10 million in federal funding for several projects focusing on brain tumor research. [Mount Sinai] Press Release

From Service to Science: NIH Shifts Focus of Mentoring Network Aimed at Boosting Grantee Diversity

As co-director of graduate affairs at the University of Chicago, Nancy Schwartz spent the past four years helping faculty members at 15 major research universities become better mentors. The project was supported by the National Research Mentoring Network, a $23 million effort that the National Institutes of Health launched after discovering an embarrassing racial gap in who gets NIH grants. [ScienceInsider] Editorial

UK Group Tackles Reproducibility in Research

Last month, ten UK universities became part of the UK Reproducibility Network, joining a network that already includes stakeholders such as the Academy of Medical Sciences, Research Libraries UK, the National Institute for Biological Standards and Control, journals including Nature and PLOS, and local networks of researchers. [The Scientist] Editorial

NEW Intra- and Intercellular Mechanisms of Aging
February 9-13, 2020
Vancouver, British Columbia, Canada

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NEW Research Associate – Neural Stem Cells and Neurophysiology (University Hospital Carl Gustav Carus Dresden)

Research Associate – Neurodegenerative Disease (Cardiff University)

Research Cognitive Neurologist (University Health Network)

Postdoctoral Research Position – Neural Reprogramming and Repair (Rosalind Franklin University of Medicine and Science)

Postdoctoral Research Fellow – Neural Stem Cell Genome Integrity in Brain Development and Diseases (German Cancer Research Center in the Helmholtz Association)

Assistant or Associate Professor – Neural Repair (Burke Neurological Institute)

Postdoctoral Associate – Neuron Diversity Mechanisms in Brain Development (Howard Hughes Medical Institute)

Postdoctoral Associate – Glia and Neuron Interaction (Howard Hughes Medical Institute)

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Faculty Positions – Brain Disorders (IDG/McGovern Institute for Brain Research)

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