Neural Cell News Volume 11.14 | Apr 12 2017

TOP STORY

Induction of Functional Dopamine Neurons from Human Astrocytes In Vitro and Mouse Astrocytes in a Parkinson’s Disease Model

Investigators describe an alternative strategy for Parkinson’s disease in which dopamine neurons are generated by direct conversion of astrocytes. Using three transcription factors, NEUROD1, ASCL1 and LMX1A, and the microRNA miR218, collectively designated NeAL218, they reprogrammed human astrocytes in vitro, and mouse astrocytes in vivo, into induced dopamine neurons. [Nat Biotechnol] Abstract | Press Release

(Ranked by impact factor of the journal)

A Novel Perivascular Cell Population in the Zebrafish Brain

The authors describe a novel perivascular cell population closely associated with blood vessels on the zebrafish brain. Based on similarities in their morphology, location, and scavenger behavior, these cells appear to be the zebrafish equivalent of cells variably characterized as fluorescent granular perithelial cells, perivascular macrophages, or ‘Mato Cells’ in mammals. [eLife] Full Article | Press Release

NSPc1 Promotes Cancer Stem Cell Self-Renewal by Repressing the Synthesis of All-Trans Retinoic Acid via Targeting RDH16 in Malignant Glioma

Investigators found that nervous system polycomb 1 (NSPc1) was highly expressed in stem cell-like glioma cells (SLCs). Knockdown of NSPc1 in SLCs resulted in impaired neurosphere formation and self-renewal abilities, down-regulated expression of stemness markers such as NESTIN, CD133 and SOX2, and decreased capacity to propagate subcutaneous xenografts. [Oncogene] Abstract

PARP Inhibitors Enhance Replication Stress and Cause Mitotic Catastrophe in MYCN-Dependent Neuroblastoma

Scientists showed that high poly (ADP-ribose) polymerases (PARP)1 and PARP2 expression is significantly associated with high-risk neuroblastoma cases and poor survival, highlighting its previously unrecognized prognostic value for human neuroblastoma. In vitro, PARP1 and 2 are abundant in MYCN amplified and MYCN-overexpressing cells. In this context, PARP inhibitors with high ‘PARP trapping’ potency, such as olaparib or talazoparib, yield DNA damage and cell death preceded by intense signs of replication stress. [Oncogene] Abstract

STIM1 Ca²⁺ Sensor Control of L-type Ca²⁺-Channel-Dependent Dendritic Spine Structural Plasticity and Nuclear Signaling

Researchers showed in hippocampal neurons that L-type Ca²⁺ channels (LTCC) inhibition by the endoplasmic reticulum (ER) Ca²⁺ sensor, stromal interaction molecule 1, is engaged by the neurotransmitter glutamate, resulting in regulation of spine ER structure and nuclear signaling by the NFATc3 transcription factor. [Cell Rep] Full Article | Graphical Abstract

Modeling Developmental and Tumorigenic Aspects of Trilateral Retinoblastoma via Human Embryonic Stem Cells

The authors developed a model to study the role of retinoblastoma-1 RB1 in early development and tumor formation by generating RB1-null human embryonic stem cells (hESCs) using CRISPR/Cas9. RB1^−/− hESCs initiated extremely large teratomas, with neural expansions similar to those of trilateral retinoblastoma tumors, in which retinoblastoma is accompanied by intracranial neural tumors. [Stem Cell Reports] Full Article | Graphical Abstract

Exfoliated Human Olfactory Neuroepithelium: A Source of Neural Progenitor Cells

Scientists proposed the establishment and characterization of neural progenitor cells cultures derived from the human olfactory neuroepithelium, using non-invasive procedures. Cells were recovered and kept as neurospheres under serum-free conditions. The neural progenitor origin of these neurospheres was determined by immunocytochemistry and qPCR. Their ability for self-renewal and multipotency was analyzed by clonogenic and differentiation assays, respectively. In the cultures, the olfactory neuroepithelium cells preserved the phenotype of the neurospheres. [Mol Neurobiol] Abstract

Systemic Administration of Induced Neural Stem Cells Regulates Complement Activation in Mouse Closed Head Injury Models

Researchers explored the role of systemically delivered induced neural stem cells (iNSCs) in complement activation following central nervous system injury. Their data showed that iNSC grafts decreased the levels of sera C3a and C5a and down-regulated the expression of C3d, C9, active caspase-3 and bax in the brain, kidney and lung tissues of closed head injury mice. [Sci Rep] Full Article

PID1 Increases Chemotherapy-Induced Apoptosis in Medulloblastoma and Glioblastoma Cells in a Manner that Involves NFκB

The authors hypothesized that phosphotyrosine interaction domain containing 1 (PID1) sensitizes brain tumors to therapy. They found that PID1 increased the apoptosis induced by cisplatin and etoposide in medulloblastoma and glioblastoma cell lines. PID1 siRNA diminished cisplatin-induced apoptosis, suggesting that PID1 is required for cisplatin-induced apoptosis. [Sci Rep] Full Article | Press Release

Multichannel Polymer Scaffold Seeded with Activated Schwann Cells and Bone Mesenchymal Stem Cells Improves Axonal Regeneration and Functional Recovery after Rat Spinal Cord Injury

Scientists used a combinatorial strategy to promote axonal regeneration and functional recovery after spinal cord injury was evaluated in adult rats. The rats were subjected to a complete transection in the thoracic spinal cord, and multichannel scaffolds seeded with activated Schwann cells and/or rat bone marrow-derived mesenchymal stem cells were acutely grafted into the transection gap. [Acta Pharmacol Sin] Abstract

Genetic and Activity-Dependent Mechanisms Underlying Interneuron Diversity

A major objective in neurobiology has been to understand the molecular determinants that link neural birth to terminal specification and functional connectivity, a task that is especially daunting in the case of cortical interneurons. Scientists discuss a wealth of recent findings that have advanced our understanding of the developmental mechanisms that contribute to the diversification of interneurons and suggest areas of particular promise for further investigation. [Nat Rev Neurosci] Abstract

Biomimetic Nanofibrous Scaffolds for Neural Tissue Engineering and Drug Development

The authors review the current techniques in fabricating biomimetic nanofibrous scaffolds for neural tissue engineering, and describe the impact of nanofiber components on the properties of scaffolds and their uses in therapeutic models and drug development. They also discuss the current challenges and future directions of applying 3D printing and microfluidic technologies in neural tissue engineering. [Drug Discov Today] Abstract

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

Valeo Pharma and Zambon Form Partnership for Parkinson’s Disease Treatment Xadago^® (Safinamide) in Canada

Zambon S.p.A. and Valeo Pharma Inc. announced a strategic agreement to commercialize Xadago^® for the treatment of Parkinson’s disease in Canada. [Valeo Pharma] Press Release

Neuralstem Expands Phase I Safety Trial of NSI-566 Neural Stem Cells in Spinal Injury

Neuralstem, Inc. announced that a new cohort of four patients will be added to its ongoing Phase I human clinical trial evaluating the safety and feasibility of using NSI-566 spinal cord-derived neural stem cells to repair chronic spinal cord injury. The amended protocol was approved by the U.S. Food and Drug Administration and the Institutional Review Board at the study site, University of California San Diego. [Neuralstem, Inc.] Press Release

Mission Therapeutics and University of Oxford Awarded Research Grant from the Michael J. Fox Foundation

Mission Therapeutics announced that it has been awarded a grant from the Michael J. Fox Foundation for Parkinson’s Research. This research grant will support the testing of Mission Therapeutics’ potent and selective USP30-targeted inhibitors in translationally relevant stem cell-derived Parkinson’s disease models developed by Professor Richard Wade-Martins and his research group at the University of Oxford. [Mission Therapeutics] Press Release

U.S. Report Calls for Research Integrity Board

A new report from the National Academies of Sciences, Engineering, and Medicine entitled Fostering Integrity in Research recommends that universities and scientific societies create, operate, and fund a new, independent, nongovernmental Research Integrity Advisory Board. [ScienceInsider] Editorial

Billion-Dollar Boost Sought for Canadian Science

The Canadian government should increase its support for fundamental science by more than a third, from Can $3.5 billion per year to Can $4.8 billion, according to a long-awaited independent review of the country’s research priorities and funding. Although Canada’s three major granting agencies and a research-support fund received a record-breaking Can $95-million boost in 2016, their funding stayed flat in the 2017 budget that the government released last month. The science review recommends increases for those three agencies, as well as a handful of other programmes, that would amount to Can $325 million per year for four years. [Nature News] Editorial

NEW Gordon Research Conferences: Excitatory Synapses & Brain Function
May 28-June 2, 2017
Les Diablerets, Switzerland

NEW Gordon Research Conferences: Modulation of Neural Circuits & Behavior
June 4-9, 2017
Newry, Maine,, United States

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

NEW Postdoctoral Position(s) – Developmental Neurobiology (Children’s National Health Systems)

NEW Postdoctoral Position(s) – Visual Neuroscience (Yale University)

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)

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)

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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