Neural Cell News Volume 11.00 | Jan 4 2017

TOP STORY

Induction of Expansion and Folding in Human Cerebral Organoids

Scientists showed that increasing neural progenitors proliferation induces expansion and folding in an in vitro model of human corticogenesis. Deletion of PTEN stimulates proliferation and generates significantly larger and substantially folded cerebral organoids. This genetic modification allows sustained cell cycle re-entry, expansion of the progenitor population, and delayed neuronal differentiation, all key features of the developing human cortex. [Cell Stem Cell] Abstract | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

Mitochondrial PKM2 Regulates Oxidative Stress-Induced Apoptosis by Stabilizing Bcl2

Researchers uncovered a novel mechanism through which mitochondrial pyruvate kinase M2 isoform (PKM2) phosphorylates Bcl2 and inhibits apoptosis directly, highlighting the essential role of PKM2 in ROS adaptation of cancer cells. [Cell Res] Full Article

Nipbl Interacts with Zfp609 and the Integrator Complex to Regulate Cortical Neuron Migration

Scientists identified Nipbl as a functional interaction partner of the neural transcription factor Zfp609 in brain development. Depletion of Zfp609 or Nipbl from cortical neural progenitors in vivo is detrimental to neuronal migration. Zfp609 and Nipbl overlap at genomic binding sites independently of cohesin and regulate genes that control cortical neuron migration. They found that Zfp609 and Nipbl interact with the Integrator complex, which functions in RNA polymerase 2 pause release. [Neuron] Full Article

A Driver Role for GABA Metabolism in Controlling Stem and Proliferative Cell State through GHB Production in Glioma

The authors showed that metabolite profiling of human adult glioblastoma stem-like cells upon loss of their tumorigenicity revealed a switch in the catabolism of the GABA neurotransmitter toward enhanced production and secretion of its by-product 4-hydroxybutyrate (GHB). This switch was driven by succinic semialdehyde dehydrogenase (SSADH) downregulation. Enhancing GHB levels via SSADH downregulation or GHB supplementation triggered cell conversion into a less aggressive phenotypic state. GHB affected adult glioblastoma cells with varying molecular profiles, along with cells from pediatric pontine gliomas. [Acta Neuropathol] Full Article

Nrf2 Mitigates LRRK2- and α-Synuclein–Induced Neurodegeneration by Modulating Proteostasis

Researchers determined if activating nuclear factor erythroid 2-related factor (Nrf2), a potential therapeutic target for neurodegeneration, could reduce Parkinson’s disease-associated neuron toxicity by modulating the protein homeostasis network. [Proc Natl Acad Sci USA] Abstract | Press Release

Inhibition of Radiation-Induced Glioblastoma Invasion by Genetic and Pharmacological Targeting of MDA-9/Syntenin

Melanoma differentiation-associated gene 9 [MDA-9/Syntenin; syndecan-binding protein (SDCBP)], a highly conserved double-PDZ domain-containing scaffolding protein, is robustly expressed in human-derived glioblastoma multiforme (GBM) cell lines and patient samples, with expression increasing with tumor grade and correlating with shorter survival times and poorer response to radiotherapy. The authors showed knockdown of MDA-9/Syntenin sensitizes GBM cells to radiation, reducing postradiation invasion gains. Radiation induces Src and EGFRvIII signaling, which is abrogated through MDA-9/Syntenin down-regulation. [Proc Natl Acad Sci USA] Abstract | Press Release

TRIM28 Controls a Gene Regulatory Network Based on Endogenous Retroviruses in Human Neural Progenitor Cells

Scientists found a region- and developmental stage-specific expression pattern of endogenous retroviruses (ERVs) in the developing human brain, which is linked to a transcriptional network based on ERVs. They demonstrated that almost 10,000, primarily primate-specific, ERVs act as docking platforms for the co-repressor protein TRIM28 in human neural progenitor cells, which results in the establishment of local heterochromatin. [Cell Rep] Full Article | Graphical Abstract

Cytosine-5 RNA Methylation Regulates Neural Stem Cell Differentiation and Motility

The authors showed that NSUN2 is expressed in early neuroepithelial progenitors of the developing human brain, and its expression is gradually reduced during differentiation of human neuroepithelial stem cells in vitro. In the developing Nsun2^−/− mouse cerebral cortex, intermediate progenitors accumulate and upper-layer neurons decrease. [Stem Cell Reports] Full Article

Hippocalcin Promotes Neuronal Differentiation and Inhibits Astrocytic Differentiation in Neural Stem Cells

Investigators reported that, in addition to inducing neurogenesis, hippocalcin (HPCA) inhibits astrocytic differentiation of neural stem cells. It promotes neurogenesis by regulating protein kinase Cα (PKCα) activation by translocating to the membrane and binding to phosphoinositide-dependent protein kinase 1, which induces PKCα phosphorylation. They also found that phospholipase D1 is implicated in the HPCA-mediated neurogenesis pathway; this enzyme promotes dephosphorylation of signal transducer and activator of transcription 3, which is necessary for astrocytic differentiation. [Stem Cell Reports] Full Article

Zika Virus Infection Induces Mitosis Abnormalities and Apoptotic Cell Death of Human Neural Progenitor Cells

To investigate the deleterious effects of Zika virus (ZIKV) infection, the authors used human neural progenitor cells (NPC), derived from induced pluripotent stem cells (iPSC). They found that NPC are highly susceptible to ZIKV and the infection results in cell death. ZIKV infection led to a marked reduction in cell proliferation, ultrastructural alterations and induction of autophagy. [Sci Rep] Full Article

Characterization of Dorsal Root Ganglion Neurons Cultured on Silicon Micro-Pillar Substrates

Investigators focused on characterization of dorsal root ganglion (DRG) neurons cultured on silicon micro-pillar substrates with the ultimate goal of designing micro-electrode arrays for successful electrophysiological recordings of DRG neurons. [Sci Rep] Full Article

Neurons Derived from Different Brain Regions Are Inherently Different In Vitro: A Novel Multiregional Brain-on-a-Chip

Scientists demonstrated that rat neurons from different brain regions exhibit unique profiles regarding their cell composition, protein expression, metabolism, and electrical activity in vitro. [J Neurophysiol] Abstract

Stem Cells and Labeling for Spinal Cord Injury

The authors review the current findings on stem cells (SCs)-based therapeutic strategies, and they compare different SCs labeling approaches for spinal cord injury. [Int J Mol Sci] Abstract | Graphical Abstract

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

GeNeuro Provides Update on GNbAC1 Multiple Sclerosis Clinical Program

GeNeuro provided an update on GNbAC1, its multiple sclerosis drug candidate. GNbAC1, the first drug candidate directly targeting a potential cause of multiple sclerosis, is a monoclonal antibody designed to neutralize MSRV-Env, a pathogenic protein which has been associated with both the inflammatory and neurodegenerative components of the disease. [GeNeuro SA] Press Release

Albert Einstein College of Medicine Receives Major Federal Grant for Research into Intellectual and Developmental Disabilities

The National Institutes of Health has awarded Albert Einstein College of Medicine a five-year, $6 million grant to fund the Rose F. Kennedy Intellectual and Developmental Disabilities Research Center. [Albert Einstein College of Medicine] Press Release

US Scientists Fear New Restrictions on Fetal-Tissue Research

House Republicans conclude that tissue from aborted fetuses is of limited value for research and seek to reduce funding. [Nature News] Editorial

Argentina’s Researchers Occupy Science Ministry

Hundreds of young researchers occupied Argentina’s science ministry in Buenos Aires last month, angry at budget cuts that they say have denied them permanent jobs at the country’s National Scientific and Technical Research Council. The occupation was the most extreme action yet by Argentinian scientists after months of protests at last year’s budget, the first under President Mauricio Macri. And the occupation seems to have paid off, in part: many of those involved have been offered extensions to their fellowships. [Nature News] Editorial

Scientists in Germany, Peru and Taiwan to Lose Access to Elsevier Journals

Thousands of scientists in Germany, Peru and Taiwan are preparing for a new year without online access to journals from the Dutch publishing giant Elsevier. Contract negotiations in both Germany and Taiwan broke down in December, while Peru’s government has cut off funding for a licence. [Nature News] Editorial

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

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

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

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

Neuroscientist – Precision Neurotherapeutics (University of California, Davis)

Postdoctoral Research Scholar – Neurodegenerative Diseases (Buck Insititute)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

Postdoctoral Fellow – Neurobiology of Hunger And Other Homestatic Drivers (Beth Israel Deaconess Medical Center/Harvard Medical School)

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

Postdoctoral Researcher – Alzheimer’s Disease (University of Arkansas)

Postdoctoral Fellow – Genetic and Epigenetic Features Parkinson’s and Alzheimer’s Diseases (Van Andel Research Institute)

Assistant Professor (Tenure) -)

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in Neural Cell News? Click here to submit!

Comments or suggestions? Submit your feedback here.