Neural Cell News Volume 12.18 | May 9 2018

TOP STORY

The Joy of Neurons: A Simplified ‘Cookbook’ for Engineering Brain Cells to Study Disease

Scientists devised what they call a “neuronal cookbook” for turning skin cells into different types of neurons. The research opens the door to studying common brain conditions such as autism, schizophrenia, addiction and Alzheimer’s disease under reproducible conditions in a dish. [Press release from The Scripps Research Institute discussing online prepublication in Nature] Press Release | Abstract

(Ranked by impact factor of the journal)

Single-Cell Transcriptomics and Fate Mapping of Ependymal Cells Reveals an Absence of Neural Stem Cell Function

Single-cell RNA-seq revealed that ependymal cells are enriched for cilia-related genes and share several stem-cell-associated genes with neural stem or progenitors. Under in vivo and in vitro neural-stem- or progenitor-stimulating environments, ependymal cells failed to demonstrate any suggestion of latent neural-stem-cell function. [Cell] Abstract | Press Release | Graphical Abstract

Efficient Generation of CA3 Neurons from Human Pluripotent Stem Cells Enables Modeling of Hippocampal Connectivity In Vitro

The authors report a comprehensive and efficient differentiation paradigm for human induced pluripotent stem cells that generate multiple CA3 pyramidal neuron subtypes as detected by single-cell RNA sequencing. [Cell Stem Cell] Abstract | Graphical Abstract

Survival of Syngeneic and Allogeneic iPSC-Derived Neural Precursors after Spinal Grafting in Minipigs

Investigators demonstrated that syngeneic porcine induced pluripotent stem cell (iPSC)-derived neural precursor cell transplantation to the spinal cord in the absence of immunosuppression is associated with long-term survival and neuronal and glial differentiation. [Sci Transl Med] Abstract | Press Release

Filopodia Conduct Target Selection in Cortical Neurons Using Differences in Signal Kinetics of a Single Kinase

Researchers demonstrated in cortical neurons that a single cue is sufficient for dendritic filopodia to reject or select specific axonal contacts for elaboration as synaptic sites. [Neuron] Abstract | Graphical Abstract

RNF12 X-Linked Intellectual Disability Mutations Disrupt E3 Ligase Activity and Neural Differentiation

Scientists showed that RNF12 catalytic activity is required for proper stem cell maintenance and neural differentiation, and this is disrupted by patient-associated X-linked intellectual disability mutation. [Cell Rep] Full Article | Graphical Abstract

CDK5 Inhibition Resolves PKA/cAMP-Independent Activation of CREB1 Signaling in Glioma Stem Cells

Pharmaceutical inhibition of CDK5 prevents glioma stem cell self-renewal in vitro and in xenografted tumors, at least partially by suppressing CREB1 activation independently of PKA/cAMP. [Cell Rep] Full Article | Graphical Abstract

Inhibition of GPR158 by MicroRNA-449a Suppresses Neural Lineage of Glioma Stem/Progenitor Cells and Correlates with Higher Glioma Grades

GPR158 promoted glioma stem cell differentiation and induced apoptosis and was highest expressed in the cerebral cortex and in oligodendrogliomas, lower in IDH mutant astrocytomas and lowest in the most malignant form of glioma, IDH wild-type glioblastoma. [Oncogene] Full Article

Loss of MECP2 Leads to Activation of P53 and Neuronal Senescence

To determine the role for mutations of MECP2 in Rett syndrome, investigators generated isogenic lines of human induced pluripotent stem cells, neural progenitor cells, and neurons from patient fibroblasts with and without MECP2 expression in an attempt to recapitulate disease phenotypes in vitro. [Stem Cell Reports] Full Article

Antibody-Antisense Oligonucleotide Conjugate Downregulates a Key Gene in Glioblastoma Stem Cells

The authors developed antibody-antisense oligonucleotide (AON) conjugates to target and reduce DRR/FAM107A expression. [Mol Ther Nucleic Acids] Full Article

A Novel 2‐Phenylamino‐Quinazoline‐Based Compound Expands the Neural Stem Cell Pool and Promotes the Hippocampal Neurogenesis and the Cognitive Ability of Adult Mice

Researchers found that a novel compound, N2‐(4‐isopropylphenyl)‐5‐(3‐methoxyphenoxy)quinazoline‐2,4‐diamine, enhanced the self‐renewal capability of neural stem cells in vitro and in vivo. [Stem Cells] Abstract

Alterations in Cell Motility, Proliferation, and Metabolism in Novel Models of Acquired Temozolomide Resistant Glioblastoma

Investigators created and characterized two new glioblastoma cell lines resistant to temozolomide (TMZ) in vitro, based on the 8MGBA and 42MGBA cell lines. Analysis of the TMZ resistant variants in conjunction with their parental, sensitive cell lines showed that acquisition of TMZ resistance is accompanied by broad phenotypic changes, including increased proliferation, migration, chromosomal aberrations, and secretion of cytosolic lipids. [Sci Rep] Full Article

Human Cortex Spheroid with a Functional Blood Brain Barrier for High-Throughput Neurotoxicity Screening and Disease Modeling

Scientists report a 3D spheroid model of the blood brain barrier comprising all major cell types, including neurons, microglia and oligodendrocytes, to recapitulate more closely normal human brain tissue. [Sci Rep] Full Article

Insights into C9ORF72-Related ALS/FTD from Drosophila and iPSC Models

Approaches that combine the genetic power of Drosophila and the disease relevance of induced pluripotent stem cell (iPSC)-derived patient neurons unravel the underlying pathogenic mechanisms and help identify potential therapeutic targets in C9ORF72-ALS/FTD. [Trends Neurosci] Abstract

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

The Power of Biomarkers and Efficacy of Vaccine Responses among Patients Treated with Newly Approved Multiple Sclerosis Drug

In March 2017, the FDA approved ocrelizumab as the first treatment for both relapsing and progressive forms of MS. Neurologist Amit Bar-Or, MD, FRCPC, chief of the Multiple Sclerosis division and director for the Center for Neuroinflammation and Experimental Therapeutics, presented findings from two studies that look more deeply into the impact of ocrelizumab in these patients. [Press release from University of Pennsylvania discussing research presented at the 2018 American Academy of Neurology (AAN) Annual Meeting, Los Angeles] Press Release

BrainStorm CEO to Present

BrainStorm Cell Therapeutics Inc. announced that Chaim Lebovits, president and CEO, will present data from the company’s Phase II clinical study of NurOwn^® in ALS. [Press release from BrainStorm Cell Therapeutics Inc. discussing research to be presented at the World Advanced Therapy and Regenerative Medicine Congress, London] Press Release

Dr. Madeline Lancaster talks about her groundbreaking work generating ‘mini-brains’. Watch Now

FORMA Therapeutics and the University of Oxford Announce Multi-Year Collaboration to Advance the Development of Deubiquitinating Enzyme (DUB) Inhibitors for the Treatment of Neurodegenerative Diseases

FORMA Therapeutics and the University of Oxford announced that they have entered into a collaboration and license agreement to identify, validate and develop DUB inhibitors for the treatment of neurodegenerative diseases. [FORMA Therapeutics (Business Wire Inc.)] Press Release

£18 Million Fund to Tackle Six Biggest Themes in Brain Tumor Research Launched

The Cancer Research UK Brain Tumor Awards have been launched in partnership with The Brain Tumor Charity. The aim of the awards is to help advance the understanding about the biology of the disease and the challenges translating discoveries into treatments. [Cancer Research UK] Press Release

Cure Brain Cancer Foundation Launches New Program to Find Cures Faster by Boosting Australian Research Capacity

Cure Brain Cancer Foundation launched its Capacity Building Program – a new initiative to rapidly increase brain cancer research capacity in Australia to more quickly find cures for the disease. The program will do so by encouraging more world-class researchers to work in brain cancer, while increasing the resources at their disposal, beginning with two new Infrastructure Grants. [Cure Brain Cancer Foundation] Press Release

Biohaven Initiates Expanded Access Program for Sublingual BHV-0223 ZYDIS^® Orally Dissolving Tablets for Patients with Amyotrophic Lateral Sclerosis (ALS)

Biohaven Pharmaceutical Holding Company Ltd. announced that it has established an expanded access program with sublingual BHV-0223, an investigational drug candidate, for patients with ALS. [Biohaven Pharmaceutical Holding Company Ltd.] Press Release

Neurotrope, in Consultation with Leading Neuroscientists, Completes the Study Design for Its Confirmatory Phase II Trial in Advanced Alzheimer’s Patients

Neurotrope, Inc. announced that Neurotrope Bioscience, Inc., its wholly-owned operating subsidiary, has completed the study design for its confirmatory Phase II clinical trial in moderate to severe Alzheimer’s disease. [Neurotrope, Inc. (PR Newswire Association LLC.)] Press Release

NIH’s Neuroscience Institute Will Limit Grants to Well-Funded Labs

Big laboratories are back in the crosshairs at the National Institutes of Health (NIH). NIH’s neurological institute plans to pare back the number of investigators it supports who have $1 million or more in NIH grants. [ScienceInsider] Editorial

Australian Budget Delivers for Science Facilities and Medical Research

The government will push to invest almost Aus$1.9 billion (US$1.4 billion) over the next 12 years in shared research infrastructure — such as microscopes, supercomputers, a marine observing system and telescopes used in myriad disciplines, from nanotechnology to oceanography. Medical research will receive an increase of $1.3 billion, to be spent on various programs and initiatives over 10 years that improve health and boost the medical industry, including $500 million for a genomics and precision-medicine initiative. [Nature News] Editorial

Animal Tests Surge under New U.S. Chemical Safety Law

The cause of the increase isn’t clear. But the new law imposes stricter requirements on a broader array of chemicals than its predecessor, including both new products and ones already on the market, and experts say Environmental Protection Agency staff may be trying to comply by gathering more test data from companies. [ScienceInsider] Editorial

NEW Keystone Symposia: Advances in Neurodegenerative Diseases Research and Therapy
June 17-21, 2018
Keystone, Colorado, United States

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

NEW Research Associate – Neural Research (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Glioma Genetics/Epigenetics (Heidelberg University)

Postdoctoral Positions – RNA Biology and Neurodegenerative Disease (Johns Hopkins University)

Research Technician – Neuroscience (Howard Hughes Medical Institute)

Postdoctoral Position – Brain Disorders (New York Medical College)

Research Fellow/Associate – Neuroscience and Diabetes (Rutgers University)

Postdoctoral Position – Bacterial Virulence Factors (University of California, Irvine)

Postdoctoral Fellow – Neural Control of Circulation (MD Anderson Cancer Center)

Postdoctoral Position – Cancer, Immunotherapy, and Fibrosis (University of Alabama at Birmingham)

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

Postdoctoral Position – Pain in Mouse Models of Spinal Cord Injury (Indiana University)

Postdoctoral Position – Spinal Cord Injury (Nanyang Technological University)

Multiple Faculty Positions – Neuroscience and Neuroengineering (Tsinghua University)

Faculty Members – Neuroscience (Mercer University)

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