Neural Cell News Volume 13.41 | Oct 23 2019

TOP STORY

Organoid Single-Cell Genomic Atlas Uncovers Human-Specific Features of Brain Development

Scientists analyzed stem cell-derived cerebral organoids using single-cell transcriptomics and accessible chromatin profiling to investigate gene-regulatory changes that are specific to humans. [Nature] Abstract | Press Release

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Glutamatergic Synaptic Input to Glioma Cells Drives Brain Tumor Progression

Researchers report a direct communication channel between neurons and glioma cells in different disease models and human tumors: functional bona fide chemical synapses between presynaptic neurons and postsynaptic glioma cells. [Nature] Abstract

High-Throughput Mapping of Long-Range Neuronal Projection Using In Situ Sequencing

The authors introduced barcoded anatomy resolved by sequencing, a multiplexed method based on RNA barcoding for mapping projections of thousands of spatially resolved neurons in a single brain and relating those projections to other properties such as gene or Cre expression. [Cell] Abstract | Graphical Abstract

Identification and Massively Parallel Characterization of Regulatory Elements Driving Neural Induction

Scientists found that changes in DNA accessibility preceded H3K27ac, which was followed by gene expression changes. Using massively parallel reporter assays to test the activity of 2,464 candidate regulatory sequences at all seven time points, they showed that many of these sequences had temporal activity patterns that correlated with their respective cell-endogenous gene expression and chromatin changes. [Cell Stem Cell] Abstract | Graphical Abstract

Age-Related Hyperinsulinemia Leads to Insulin Resistance in Neurons and Cell-Cycle-Induced Senescence

CDK5 contributed to neuronal cell death while β-catenin entered the neuronal nucleus and re-activated the cell cycle machinery. Unable to successfully divide, the neuron instead entered a senescent-like state. [Nat Neurosci] Abstract

A Modulator of Wild-Type Glucocerebrosidase Improves Pathogenic Phenotypes in Dopaminergic Neuronal Models of Parkinson’s Disease

Investigators developed a new small-molecule modulator of β-glucocerebrosidase (GCase) called S-181 that increased wild-type GCase activity in iPSC-derived dopaminergic neurons from sporadic Parkinson’s disease patients, as well as patients carrying the 84GG mutation in GBA1, or mutations in LRRK2, DJ-1, or PARKIN who had decreased GCase activity. [Sci Transl Med] Abstract

V2a Interneuron Differentiation from Mouse and Human Pluripotent Stem Cells

Researchers describe how to produce V2a interneurons from mouse and human pluripotent stem cells, as well as strategies to characterize and mature the cells for further analysis. [Nat Protoc] Abstract

Two Adhesive Systems Cooperatively Regulate Axon Ensheathment and Myelin Growth in the CNS MAYBE

Using combined morphological and molecular analyses in mice and zebrafish, the authors showed that adhesion molecules of the paranodal and the internodal segment worked synergistically using overlapping functions to regulate axonal interaction and myelin wrapping. [Nat Commun] Full Article

CRH Promotes the Neurogenic Activity of Neural Stem Cells in the Adult Hippocampus

Scientists showed that corticotropin-releasing hormone (CRH), the major mediator of mammalian stress response and a key neuromodulator in the adult brain, was necessary for hippocampal neural stem cell activity under physiological conditions. [Cell Rep] Full Article | Graphical Abstract

IRE1 Promotes Neurodegeneration through Autophagy-Dependent Neuron Death in the Drosophila Model of Parkinson’s Disease

Researchers found that inositol-requiring enzyme 1 (IRE1) was hyperactivated upon accumulation of α-synuclein in the fly photoreceptor neurons. Ectopic overexpression of IRE1 was sufficient to trigger autophagy-dependent neuron death in an XBP1-independent, JNK-dependent manner. [Cell Death Dis] Abstract

Rapid and Efficient Conversion of Human Fibroblasts into Functional Neurons by Small Molecules

Investigators report that human fibroblasts can be efficiently and directly reprogrammed into glutamatergic neuron-like cells by serially exposing cells to a combination of small molecules. [Stem Cell Reports] Full Article

Capture at the Single Cell Level of Metabolic Modules Distinguishing Aggressive and Indolent Glioblastoma Cells

Scientists analyzed public single cell RNA-sequencing data from glioblastoma surgical resections, which offered the closest available view of tumor cell heterogeneity as encountered at the time of patients’ diagnosis. [Acta Neuropathol Commun] Full Article

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Regulation of CNS Precursor Function by Neuronal Chemokines

Researchers summarize the roles of neuronally secreted chemokines and their documented ability to directly regulate the diverse functions of oligodendrocyte and neural precursor cells in the developing as well as adult normal and injured central nervous system (CNS) . [Neurosci Lett] Abstract

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Promis Neurosciences Advances Alzheimer’s Disease Program Targeting Neurotoxic Forms of Tau

ProMIS Neurosciences, Inc. continues to further develop antibody candidates that have shown selectivity for the toxic forms of tau. New pre-clinical data showed that these antibody candidates could block the spread of pathogenic tau aggregate formation in a cellular model. [ProMIS Neurosciences, Inc.] Press Release

Axsome Therapeutics Completes Patient Enrollment in the CONCERT Phase II Trial of AXS-12 in Narcolepsy

Axsome Therapeutics, Inc. announced the completion of patient enrollment in the CONCERT study, a Phase II, randomized, double-blind, placebo-controlled, crossover, trial of AXS-12 in patients with narcolepsy. [Axsome Therapeutics, Inc.] Press Release

NOXXON Enrolls First Patient in the Phase I/II Clinical Trial Combining NOX-A12 With Radiotherapy in Newly Diagnosed Brain Cancer

NOXXON Pharma N.V. announced the enrollment and first treatment of a patient with newly diagnosed brain cancer in a Phase I/II clinical trial. [NOXXON Pharma N.V.] Press Release

Female Researchers in Australia Less Likely to Win Major Medical Grants than Males

Female scientists in Australia were less likely to win a major type of medical-research grants this year than their male counterparts, despite an overhaul of the country’s science funding that was supposed to address gender inequity. [Nature News] Editorial

Trump Names Seven to Revived Presidential Science Advisory Panel

Thirty-three months after taking office, President Donald Trump has chosen a group of business leaders to advise him on science and technology policy. [ScienceInsider] Editorial

NEW 2020 Muscle Dystrophy Association Clinical and Scientific Conference
March 21-25, 2020
Orlando, Florida, United States

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

Postdoctoral Fellow – ALS Models (University College London)

Assistant Professor – The Neural Basis of Behavior (Mortimer B. Zuckerman Mind Brain Behavior Institute)

Postdoctoral Scholar – Neural Precursor Cells (University of South Florida)

Faculty Positions – Autism and Neurodevelopmental Disorders (University of South Carolina)

Assistant/Associate Professor – Pediatric Brain Tumors (Baylor College of Medicine)

Research Fellow – Neurodegenerative Disease (University College London)

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

Postdoctoral Position – Neural Cell Research (New York Medical College)

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