Neural Cell News Volume 15.09 | Mar 10 2021

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    2021-03-10 | NCN 15.09


    Neural Cell News by STEMCELL Technologies
    Vol. 15.09 – 10 March, 2021
    TOP STORY

    Population-Scale Single-Cell RNA-Seq Profiling Across Dopaminergic Neuron Differentiation

    Researchers used an efficient multiplexing strategy to differentiate 215 human induced pluripotent stem cell lines toward a midbrain neural fate, including dopaminergic neurons, and used single-cell RNA sequencing to profile over one million cells across three differentiation time points.
    [Nature Genetics]

    AbstractPress Release

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    In Vivo Reprogramming of NG2 Glia Enables Adult Neurogenesis and Functional Recovery Following Spinal Cord Injury

    Investigators showed that spinal cord injury (SCI) unveils a latent neurogenic potential of NG2+ glial cells, which could be exploited to produce new neurons and promote functional recovery after SCI.
    [Cell Stem Cell]

    AbstractPress ReleaseGraphical Abstract

    Circular RNA-Encoded Oncogenic E-Cadherin Variant Promotes Glioblastoma Tumorigenicity through Activation of EGFR–STAT3 Signaling

    The authors report an activation mechanism of EGFR signaling in glioblastoma (GBM) by a secretory E-cadherin protein variant (C-E-Cad) encoded by a circular E-cadherin RNA through multiple-round open reading frame translation. C-E-Cad variant was overexpressed in GBM and promoted glioma stem cell tumorigenicity.
    [Nature Cell Biology]

    Abstract

    APOE4 Disrupts Intracellular Lipid Homeostasis in Human iPSC-Derived Glia

    Scientists report that the E4 allele of the apolipoprotein E gene (APOE4), but not APOE3, disrupted the cellular lipidomes of human induced pluripotent stem cell (iPSC)–derived astrocytes generated from fibroblasts of APOE4 or APOE3 carriers, and of yeast expressing human APOE isoforms.
    [Science Translational Medicine]

    Abstract

    The Translocator Protein (TSPO) Is Prodromal to Mitophagy Loss in Neurotoxicity

    Both in vitro and in vivo data showed that neurotoxins, which phenotypically mimicked Parkinson’s Disease, increased TSPO to enhance cellular redox-stress, susceptibility to dopamine-induced cell death, and repression of ubiquitin-dependent mitophagy.
    [Molecular Psychiatry]

    Full Article

    Circadian Rhythms in Bipolar Disorder Patient-Derived Neurons Predict Lithium Response: Preliminary Studies

    The authors used induced pluripotent stem cells to culture neuronal precursor cells and glutamatergic neurons from bipolar disorder patients characterized for lithium responsiveness and matched controls.
    [Molecular Psychiatry]

    Abstract

    Opposing Functions of β-Arrestin 1 and 2 in Parkinson’s Disease via Microglia Inflammation and Nprl3

    β-arrestin 1 (ARRB1) ablation ameliorated whereas ARRB2 knockout aggravated, the pathological features of Parkinson’s disease, including dopaminergic neuron loss, neuroinflammation, and microglia activation in vivo, and microglia-mediated neuron damage in vitro.
    [Cell Death & Differentiation]

    Full Article

    A Specific RIP3+ Subpopulation of Microglia Promotes Retinopathy through a Hypoxia-Triggered Necroptotic Mechanism

    Scientists identified a subpopulation of microglia named sMG2, which highly expressed necroptosis-related genes Rip3 and Mlkl. Genetic and pharmacological loss of function demonstrated that hypoxia-induced microglial activation committed to necroptosis through the RIP1/RIP3-mediated pathway.
    [Proceedings of the National Academy of Sciences of the United States of America]

    Full Article

    Heterogeneity of Glial Progenitor Cells during the Neurogenesis-to-Gliogenesis Switch in the Developing Human Cerebral Cortex

    The authors found that EGFR expression began to sharply increase after gestational week 20, which corresponded to the beginning stages of human gliogenesis.
    [Cell Reports]

    Full ArticleGraphical Abstract

    Astrocyte-Derived Small Extracellular Vesicles Promote Synapse Formation via Fibulin-2-Mediated TGF-β Signaling

    Investigators report that small extracellular vesicles secreted from primary astrocytes, but not from neurons or C6 glioma cells, greatly enhanced spine and synapse formation by primary cortical neurons.
    [Cell Reports]

    Full ArticleGraphical Abstract

    Base Editing Strategy for Insertion of the A673T Mutation in APP Gene to Prevent the Development of Alzheimer’s Disease In Vitro

    Researchers hypothesized that the insertion of the A673T mutation in patients’ neurons could be an effective and sustainable method of slowing down or even stopping the progression of Alzheimer’s disease.
    [Molecular Therapy-Nucleic Acids]

    AbstractFull ArticleGraphical Abstract

    Neurog2 Directly Converts Astrocytes Into Functional Neurons in Midbrain and Spinal Cord

    Scientists adopted the AAV(2/8) delivery system to overexpress single factor Neurog2 into astrocytes and found that the majority of astrocytes were successfully converted into neuronal cells in multiple brain regions, including the midbrain and spinal cord.
    [Cell Death & Disease]

    Full Article

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    REVIEWS

    Multifaceted Microglia — Key Players in Primary Brain Tumor Heterogeneity

    Investigators place a special emphasis on the heterogeneity of the tumor-associated microglia and macrophage populations present in primary brain tumors.
    [Nature Reviews Neurology]

    Abstract

    Neurobiology of ARID1B Haploinsufficiency Related to Neurodevelopmental and Psychiatric Disorders

    Scientists examine past and present clinical and preclinical research into the neurobiological function of ARID1B. The presentation of ARID1B-related disorders is highly heterogeneous, including varying degrees of intellectual disability, autism spectrum disorder, and physical features.
    [Molecular Psychiatry]

    Abstract

    Dynamic Control of the Dopamine Transporter in Neurotransmission and Homeostasis

    The authors summarize mechanisms governing dopamine transporter (DAT) trafficking under normal physiological conditions and discuss how Parkinson’s disease-linked mutations may disturb DAT homeostasis.
    [npj Parkinson’s Disease]

    Full Article

    INDUSTRY AND POLICY NEWS

    Clene Nanomedicine Announces Achievement of 50% Enrollment in the Phase III HEALEY ALS Platform Trial

    Clene, Inc. announced that over 50% of participants have been enrolled in the HEALEY ALS Platform Trial being conducted at sites of the Northeast ALS consortium.
    [Clene, Inc.]

    Press Release

    OncoSynergy Announces First Patient Treated in First-in-Human Clinical Trial of OS2966 in Recurrent Glioblastoma

    OncoSynergy, Inc. announced that the first patient was treated in the company’s First-in-Human Phase 1Iclinical trial evaluating OS2966 for the treatment of recurrent glioblastoma at Moffitt Cancer Center in Tampa, Florida. OS2966 is a first-in-class immunotherapy, and the first ever anti-CD29 therapeutic to reach human trials.
    [OncoSynergy, Inc. (PR Newswire. LLC)]

    Press Release

    FEATURED EVENT

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    April 14 – 16, 2021
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    JOB OPPORTUNITIES

    Postdoctoral Researcher – Circuit Neuroscience

    DZNE – Bonn, Germany

    Postdoctoral Fellow – Neuropathology

    Johns Hopkins University School of Medicine – Baltimore, Maryland. United States

    Postdoctoral Fellow – Neuro-Urology

    Beth Israel Deaconess Medical Center – Boston, Massachusetts, United States

    Principal Investigator – Functional Neurobiology

    Flanders Institute for Biotechnology – Antwerp, Belgium

    Assistant Professor – Neuro-Oncology

    UC San Francisco – Location

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