Neural Cell News Volume 11.03 | Jan 25 2017

TOP STORY

Combined Small-Molecule Inhibition Accelerates the Derivation of Functional Cortical Neurons from Human Pluripotent Stem Cells

Investigators developed a small-molecule approach for accelerated induction of early-born cortical neurons. Combinatorial application of six pathway inhibitors induced post-mitotic cortical neurons with functional electrophysiological properties by day 16 of differentiation, in the absence of glial cell co-culture. The resulting neurons, transplanted at day eight of differentiation into the postnatal mouse cortex, were functional and establish long-distance projections, as shown using iDISCO whole-brain imaging. [Nat Biotechnol] Abstract

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Human iPSC-Derived Cerebral Organoids Model Cellular Features of Lissencephaly and Reveal Prolonged Mitosis of outer Radial Glia

Researchers investigated the effects of Miller-Dieker syndrome (MDS) on human progenitor subtypes that control neuronal output and influence brain topology, they analyzed cerebral organoids derived from control and MDS-induced pluripotent stem cells using time-lapse imaging, immunostaining, and single-cell RNA sequencing. [Cell Stem Cell] Abstract | Graphical Abstract

Optogenetic Demonstration of Functional Innervation of Mouse Colon by Neurons Derived from Transplanted Neural Cells

The authors demonstrated enteric neural cells transplanted into the bowel gave rise to multiple functional types of neurons that integrated and provided a functional innervation of the smooth muscle of the bowel wall. Circuits composed of both motor neurons and interneurons were established, but they found the age at which cells are isolated influences the neurotransmitter phenotype of interneurons that are generated. [Gastroenterology] Abstract

Abnormal Neurogenesis and Cortical Growth in Congenital Heart Disease

Investigators showed that the piglet subventricular zone (SVZ) resembles its human counterpart and displays robust postnatal neurogenesis. They presented evidence that SVZ neural stem/progenitor cell migrate to the frontal cortex and differentiate into interneurons in a region-specific manner. Hypoxic exposure of the gyrencephalic piglet brain recapitulated congenital heart disease-induced impaired cortical development. Hypoxia reduced proliferation and neurogenesis in the SVZ, which was accompanied by reduced cortical growth. [Sci Transl Med] Abstract | Press Release

GLUT4 Mobilization Supports Energetic Demands of Active Synapses

Scientists provide strong evidence that during action potential firing, nerve terminals rely on the glucose transporter GLUT4 as a glycolytic regulatory system to meet the activity-driven increase in energy demands. Activity at synapses triggered insertion of GLUT4 into the axonal plasma membrane driven by activation of the metabolic sensor AMP kinase. [Neuron] Abstract | Press Release

Whole-Brain 3D Mapping of Human Neural Transplant Innervation

The authors combined rabies virus-based retrograde with light sheet fluorescence microscopy to visualize transplanted cells and connected host neurons in whole-mouse brain preparations. Combined with co-registration of high-precision three-dimensional (3D) magnetic resonance imaging reference data sets, this approach enabled precise anatomical allocation of the host input neurons. [Nat Commun] Full Article

Synaptic Inputs from Stroke-Injured Brain to Grafted Human Stem Cell-Derived Neurons Activated by Sensory Stimuli

Investigators studied the synaptic inputs from the host brain to grafted cortical neurons derived from human induced pluripotent stem cells after transplantation into stroke-injured rat cerebral cortex. [Brain] Full Article | Press Release

Glioblastoma Cell Malignancy and Drug Sensitivity Are Affected by the Cell of Origin

The authors analyzed how the phenotypic state of the initially transformed cell affects mouse glioblastoma (GBM) development and essential GBM cell (GC) properties. They found that GBM induced in neural stem-cell-like glial fibrillary acidic protein-expressing cells in the subventricular zone of adult mice shows accelerated tumor development and produces more malignant GCs that are less resistant to cancer drugs, compared with those originating from more differentiated nestin- or 2,′3′-cyclic nucleotide 3′-phosphodiesterase-expressing cells. [Cell Rep] Full Article | Graphical Abstract

Oncogenes Activate an Autonomous Transcriptional Regulatory Circuit that Drives Glioblastoma

Scientists identified an SRY-related box 2 (SOX2) transcriptional regulatory network that is independent of upstream receptor tyrosine kinases and capable of driving glioma-initiating cells. They identified oligodendrocyte lineage transcription factor 2 and zinc-finger E-box binding homeobox 1, which are frequently co-expressed irrespective of driver mutations, as potential SOX2 targets. [Cell Rep] Abstract | Press Release | Graphical Abstract

Japanese Encephalitis Virus Induces Human Neural Stem/Progenitor Cell Death by Elevating GRP78, PHB and HnRNPC through ER Stress

The authors aimed to perceive the stem cell proteomic response upon viral challenge. They performed a two-dimensional gel electrophoresis-based proteomic study of the human neural stem cells (hNS1 cell line) post Japanese encephalitis virus infection and found that 13 proteins were differentially expressed. The altered proteome profile of hNS1 cell line revealed sustained endoplasmic reticulum (ER) stress, which deteriorated normal cellular activities leading to cell apoptosis. [Cell Death Dis] Full Article

Zika Virus Disrupts Molecular Fingerprinting of Human Neurospheres

Investigators describe alterations in human neurospheres derived from induced pluripotent stem cells infected with the strain of Zika virus. [Sci Rep] Full Article | Press Release

Therapeutic Potential of Induced Neural Stem Cells for Parkinson’s Disease

Scientists showed that induced neural stem cells (iNSCs) directly converted from mouse fibroblasts enhanced functional recovery in an animal model of Parkinson’s disease. The rotational behavior test was performed to assess recovery. Their results indicated that iNSC transplantation into the striatum of 6-hydroxydopamine-injected mice can significantly reduce apomorphine-induced rotational asymmetry. [Int J Mol Sci] Full Article

Surgical Repair in Humans after Traumatic Nerve Injury Provides Limited Functional Neural Regeneration in Adults

Biological optimization of Schwann cells, macrophages, and degradation enzymes have been studied due to the key roles of these components in axonal development, maintenance and response to injury. The authors discuss the roadblocks to recovery after nerve injury. These roadblocks include, but are not limited to: slow regeneration rates and specificity of target innervation, the presence of a segmental nerve defect, and degeneration of the target end-organ after prolonged periods of denervation. [Exp Neurol] Abstract

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CIRM Approves New Funding to UC San Diego Researchers Fighting Zika Virus and Cancer

The Independent Citizens Oversight Committee of the California Institute for Regenerative Medicine (CIRM) has approved a pair of $2 million awards to University of California San Diego School of Medicine researchers to advance studies of new treatments for Zika virus infections and the use of stem cell-derived natural killer cells to target ovarian cancer and other malignancies. [University of California San Diego] Press Release

Prestigious Prize Awarded to Caltech Neuroscientist

David Anderson, the Seymour Benzer Professor of Biology and a Howard Hughes Medical Institute Investigator, has been awarded the 17^th Perl-UNC Neuroscience Prize from the University of North Carolina Chapel Hill School of Medicine. [California Institute of Technology] Press Release

Flex Pharma Focuses on Phase II Clinical Programs in Severe Neurological Diseases

Flex Pharma, Inc. announced that it is prioritizing its clinical programs in the severe neurological diseases of amyotrophic lateral sclerosis, multiple sclerosis and peripheral neuropathies such as Charcot-Marie Tooth. The company intends to initiate one or two additional proof-of-concept Phase II studies in these indications in the US this year with FLX-787, its transient receptor potential ion channel activator. [Flex Pharma, Inc.] Press Release

AbbVie Initiates Phase II Clinical Trial Programs for ABBV-8E12, an Investigational Anti-Tau Antibody, in Early Alzheimer’s Disease and Progressive Supranuclear Palsy

AbbVie announced the start of two Phase II clinical trial programs to evaluate ABBV-8E12, an investigational anti-tau antibody, in patients with early Alzheimer’s disease and progressive supranuclear palsy. [AbbVie] Press Release

Candidates from Ethiopia, United Kingdom, and Pakistan Will Compete for WHO’s Top Slot

The World Health Organization (WHO) announced who will be up for election to the post of director-general in May. They are: former Ethiopian health minister and minister of foreign affairs Tedros Adhanom Ghebreyesus; British physician and United Nations official David Nabarro; and Pakistani cardiologist and former science minister Sania Nishtar. [ScienceInsider] Editorial

Memo Freezing NIH Communications with Congress Triggers Jitters

Is the National Institutes of Health (NIH) part of the clampdown by the Trump administration on communications at science agencies? That’s how some are reacting to White House directive telling NIH to halt correspondence with public officials and hold off on new policies. But some observers say the NIH directive is not unusual for a new administration. [ScienceInsider] Editorial

NEW ESMO Symposium on Signaling Pathways in Cancer 2017
March 17-18, 2017
Barcelona, Spain

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NEW Postdoctoral Training Fellow – Glioma Research (Institute of Cancer Research (ICR))

Postdoctoral Researcher – Stem Cell Differentiation (University of Oklahoma)

Research Associate – Parkinson’s Disease (University of Bristol)

Postdoctoral Positions – Stem Cell Technology/Neuroscience/Drug Discovery (University of California Davis)

PhD Position(s) – Neurosciences/Neurobiology (EU-GliaPhD)

Postdoctoral Research Position(s) – Alzheimer’s Disease (Dana-Farber Cancer Institute/Harvard Medical School)

Tenure Track Faculty – Stem Cells and Regenerative Medicine (University of Notre Dame)

Neuroscientist – Precision Neurotherapeutics (University of California Davis)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

Research Associate Position – Neural Rehabilitation Experiments (Nanyang Technological University)

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