Neural Cell News Volume 11.13 | Apr 5 2017

TOP STORY

Myt1l Safeguards Neuronal Identity by Actively Repressing Many Non-Neuronal Fates

By studying the reprogramming of mouse fibroblasts to neurons, the authors found that the pan neuron-specific transcription factor Myt1-like (Myt1l) exerts its pro-neuronal function by direct repression of many different somatic lineage programs except the neuronal program. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

Decoupling Genetics, Lineages, and Microenvironment in IDH-Mutant Gliomas by Single-Cell RNA-Seq

Researchers used single-cell RNA sequencing (scRNA-seq) to understand the differences between two types of isocitrate dehydrogenase (IDH)-mutant gliomas: astrocytoma (IDH-A) and oligodendroglioma (IDH-O). IDH-A and IDH-O are distinguished by co-occurring signature genetic events and by histopathology and are thought to recapitulate distinct glial lineages. By combining 9879 scRNA-seq profiles from 10 IDH-A tumors, 4347 scRNA-seq profiles from six IDH-O tumors, and 165 TCGA bulk RNA profiles, they deciphered differences between these two tumor types at single-cell resolution. [Science] Abstract

FUS Affects Circular RNA Expression in Murine Embryonic Stem Cell-Derived Motor Neurons

Investigators identified circular RNA (circRNAs) expressed in in vitro-derived mouse motor neurons and determined that the production of a considerable number of these circRNAs is regulated by FUS. [Nat Commun] Full Article

HBEGF Promotes Gliomagenesis in the Context of Ink4a/Arf and Pten Loss

Researchers demonstrated that heparin-binding epidermal growth factor-like growth factor (HBEGF) can initiate glioblastoma (GBM) in mice in the context of Ink4a/Arf and Pten loss, and that these tumors are similar to the classical GBM subtype observed in patients. Isogenic astrocytes from these mice showed activation not only of Egfr but also the receptor tyrosine kinases (RTKs) Axl in response to HBEGF stimulation. Deletion of either Egfr or Axl decreased the tumorigenic properties of HBEGF-transformed cells; however, only EGFR was able to rescue the phenotype in cells lacking both RTKs indicating that Egfr is required for activation of Axl in this context. [Oncogene] Abstract

An Organoid-Based Model of Cortical Development Identifies Non-Cell-Autonomous Defects in Wnt Signaling Contributing to Miller-Dieker Syndrome

Investigators used patient-specific forebrain-type organoids to investigate pathological changes associated with Miller-Dieker syndrome. Patient-derived organoids were significantly reduced in size, a change accompanied by a switch from symmetric to asymmetric cell division of ventricular zone radial glia cells. [Cell Rep] Full Article | Press Release | Graphical Abstract

Astrocyte-Shed Extracellular Vesicles Regulate the Peripheral Leukocyte Response to Inflammatory Brain Lesions

Brain injury induces a peripheral acute cytokine response that directs the transmigration of leukocytes into the brain. Because this brain-to-peripheral immune communication affects patient recovery, understanding its regulation is important. Using a mouse model of inflammatory brain injury, scientists set out to find a soluble mediator for this phenomenon. They found that extracellular vesicles shed from astrocytes in response to intracerebral injection of interleukin-1β rapidly entered into peripheral circulation and promoted the transmigration of leukocytes through modulation of the peripheral acute cytokine response. [Sci Signal] Abstract

Genetic Correction of SOD1 Mutant iPSCs Reveals ERK and JNK Activated AP1 as a Driver of Neurodegeneration in Amyotrophic Lateral Sclerosis

The authors combined induced pluripotent stem cells (iPSCs)-based disease modeling with genome engineering and deep RNA sequencing to identify pathways dysregulated by mutant SOD1 in human motor neuron. [Stem Cell Reports] Full Article

Sporadic ALS Astrocytes Induce Neuronal Degeneration In Vivo

It is not known if astrocytes from sporadic amyotrophic lateral sclerosis (sALS) patients cause motor neurons (MN) degeneration in vivo and whether the effect is specific to MNs. By transplanting spinal neural progenitors, derived from sALS and healthy induced pluripotent stem cells, into the cervical spinal cord of adult SCID mice for nine months, researchers found that differentiated human astrocytes were present in large areas of the spinal cord, replaced endogenous astrocytes, and contacted neurons to a similar extent. [Stem Cell Reports] Full Article

Hypoxia-Mediated Epigenetic Regulation of Stemness in Brain Tumor Cells

Activation of pluripotency regulatory circuit is an important event in solid tumor progression and the hypoxic microenvironment is known to enhance the stemness feature of some cells. The authors demonstrated the role of hypoxia-mediated epigenetic modifications in regulating expression of core pluripotency factors, OCT4 and NANOG, in glioma cells. [Stem Cells] Abstract

Cell-Based Therapy Using miR-302-367 Expressing Cells Represses Glioblastoma Growth

MicroRNA (miR)-302-367 cell-to-cell transfer resulted in the inhibition of its targets such as CXCR4/SDF1, SHH, cyclin D, cyclin A and E2F1. Orthotopic xenograft of miR-302-367-expressing cells together with glioblastoma stem-like cells efficiently altered the tumor development in mice brain. [Cell Death Dis] Full Article

Messenger RNAs Localized to Distal Projections of Human Stem Cell Derived Neurons

Scientists used compartmentalized microfluidic chambers to characterize the transcriptome of distal projections of human embryonic stem cells differentiated using a protocol which enriched for glutamatergic neurons. Using gene expression analysis, they identified mRNAs proportionally enriched in these projections, representing a functionally unique local transcriptome as compared to the human neuronal transcriptome inclusive of somata. [Sci Rep] Full Article

An Update on Stem Cell Biology and Engineering for Brain Development

An update on the transition from 2D to 3D cultures and current organoid (mini-brain) cultures are reviewed to give the stem cell and developmental engineering communities an up-to-date account of the progress and future perspectives for modeling of central nervous system disease and brain development in vitro. [Mol Psychiatry] Abstract

Brain Cancer Stem Cells in Adults and Children: Cell Biology and Therapeutic Implications

Scientists discuss progress in cancer stem cell biology as it relates to targeted therapies which may be uniquely different between pediatric and adult brain tumors. Studies to date suggest that pediatric brain tumors may benefit more from genetic and epigenetic targeted therapies, while combination treatments aimed specifically at multiple molecular pathways may be more effective in treating adult brain tumors which seem to have a greater propensity towards microenvironmental interactions. [Neurotherapeutics] Abstract

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

Sangamo Therapeutics Announces Presentation of New Data Demonstrating Significant Reduction of Tau Expression Using Proprietary ZFP Gene Regulation Technology

Sangamo Therapeutics, Inc. announced the presentation of new human in vitro and animal model data demonstrating significant reduction of tau mRNA and tau protein expression using the company’s zinc finger protein transcription factor-mediated gene regulation technology. These results are the first evidence of a tau lowering agent demonstrating efficacy on neuritic dystrophy in an amyloid mouse model of Alzheimer’s disease. [Press release from Sangamo Therapeutics, Inc. discussing research presented at the 13^th International Conference on Alzheimer’s & Parkinson’s Diseases, Vienna] Press Release

Alzheon Presents Data to Support Selection of Patients with Mild Alzheimer’s Disease for Pivotal Study of ALZ-801 Using Precision Medicine Approach

Alzheon, Inc. announced the results from studies of ALZ-801 and its active molecule, tramiprosate. The new clinical data and analyses support Alzheon’s study design for the pivotal clinical program for ALZ-801, a first-in-class, oral amyloid-targeted medicine, in a genetically-defined population of patients at the mild stage of Alzheimer’s disease, with ongoing amyloid accumulation. [Press release from Alzheon, Inc. discussing research presented at the 13^th International Conference on Alzheimer’s and Parkinson’s Diseases, Vienna] Press Release

Bristol-Myers Squibb Announces Results from CheckMate-143, a Phase III Study of Opdivo (Nivolumab) in Patients with Glioblastoma Multiforme

Bristol-Myers Squibb announced that CheckMate -143, a randomized Phase III clinical trial evaluating the efficacy and safety of Opdivo in patients with first recurrence of glioblastoma multiforme, did not meet its primary endpoint of improved overall survival over bevacizumab monotherapy. [Press release from Bristol-Myers Squibb Company discussing research to be presented at the 2017 World Federation of Neuro-Oncology Societies (WFNOS) meeting, Zurich] Press Release

Parker Institute for Cancer Immunotherapy, Bristol-Myers Squibb and the Cancer Research Institute Announce Collaboration to Accelerate Immuno-Oncology Research

The Parker Institute for Cancer Immunotherapy, Bristol-Myers Squibb Company and the Cancer Research Institute announced a multi-year clinical research collaboration to coordinate and rapidly initiate clinical Immuno-Oncology studies across the Parker Institute and CRI networks. [Bristol-Myers Squibb Company] Press Release

Researchers Named Outstanding Investigators by the National Cancer Institute

The National Cancer Institute has named professor of dermatology Howard Chang, MD, PhD, and professor of oncology Ronald Levy, MD, as recipients of the institute’s Outstanding Investigator Awards for 2016. [Stanford University] Press Release

Brazilian Scientists Reeling as Federal Funds Slashed by Nearly Half

Brazilian scientists have been left horrified by a 44% slash to the federal science budget, announced by the country’s government. This will leave the Ministry of Science, Technology, Innovations and Communications with its lowest budget in at least 12 years at just 2.8 billion reais, equivalent to US $898 million — a 2.2 billion reais cut from the five billion reais of funding that the government had originally proposed for 2017. [Nature News] Editorial

Genetic Details of Controversial ‘Three-Parent Baby’ Revealed

When a US fertility clinic revealed last year that it had created a baby boy using a controversial technique that mixes DNA from three people, scientists were quick to raise the alarm. Some objected on ethical grounds, and others questioned the scientific claims made by the clinic’s leader, physician John Zhang. [Nature News] Editorial

Few U.S. Animal Inspections Are Being Posted

The Donald Trump administration appears to have reversed its decision to remove from public sight the results of past government inspections of animal research facilities. But getting hold of new inspection reports is proving to be another matter. An animal welfare researcher has found that only four reports have been posted during the first quarter of 2017. [ScienceInsider] Editorial

NEW European Stroke Conference (ESC)
May 24-26, 2017
Berlin, Germany

NEW 11^th Annual Canadian Neuroscience Meeting
May 28-31, 2017
Montreal, Canada

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

NEW Postdoctoral Fellow – Spinal Cord Injury Repair (Burke Medical Research Institute Cornell)

Associate/Full Professor – Regenerative Medicine (University Of Florida)

Postdoctoral Fellow/Experienced Scientist – Stem Cells and Epigenetics (University of Michigan)

Assistant/Associate Professor – Canada Research Chair in Mental Health (University of Alberta)

Senior Scientist – Cognitive Neurophysiology (Forschungszentrum Jülich – FZJ – Helmholtz Association)

Postdoctoral Fellow – Stem Cell Dynamics in the Adult Hippocampus (The Francis Crick Institute)

Postdoctoral Research Associate – Developmental Neuroscience (University of Nebraska Medical Center)

PhD Student and Postdoctoral Positions – Molecular and Cellular Biology/Systems Biology/Neurobiology (University of Fribourg)

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

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)

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