Neural Cell News Volume 11.02 | Jan 18 2017

TOP STORY

Neurotoxic Reactive Astrocytes Are Induced by Activated Microglia

The authors showed that a subtype of reactive astrocytes, which they termed A1, is induced by classically activated neuroinflammatory microglia. They showed that activated microglia induce A1 astrocytes by secreting Il-1α, TNF and C1q, and that these cytokines together are necessary and sufficient to induce A1 astrocytes. A1 astrocytes lose the ability to promote neuronal survival, outgrowth, synaptogenesis and phagocytosis, and induce the death of neurons and oligodendrocytes. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

Glioblastoma Cancer Stem Cells Evade Innate Immune Suppression of Self-Renewal through Reduced TLR4 Expression

Investigators report that self-renewing cancer stem cells (CSCs) in glioblastoma have low toll-like receptor 4 (TLR4) expression that allows them to survive by disregarding inflammatory signals. Their findings provide a mechanism through which CSCs persist in hostile environments because of an inability to respond to inflammatory signals. [Cell Stem Cell] Abstract | Graphical Abstract

Immunosuppression via Loss of IL2rγ Enhances Long-Term Functional Integration of hESC-Derived Photoreceptors in the Mouse Retina

Scientists examined the degree to which immune rejection contributes to disappointing outcomes using an immunodeficient IL2 receptor γ (IL2rγ)-null mouse model. Their results showed that prevention of cell rejection in the normal and degenerating retinal environment significantly improves long-term survival and integration of hESC-derived donor retinal cells. Transplanted cells are able to differentiate into mature photoreceptors expressing various opsins and can functionally integrate into congenitally blind mice. [Cell Stem Cell] Abstract | Graphical Abstract

α-Synuclein Binds and Sequesters PIKE-L into Lewy Bodies, Triggering Dopaminergic Cell Death via AMPK Hyperactivation

The authors showed that α-synuclein binds phosphoinositide-3 kinase enhancer L (PIKE-L) in a phosphorylation-dependent manner and sequesters it in Lewy bodies, leading to dopaminergic cell death via AMP-activated protein kinase (AMPK) hyperactivation. [Proc Natl Acad Sci USA] Abstract

Tissue Engineering the Mechanosensory Circuit of the Stretch Reflex Arc with Human Stem Cells: Sensory Neuron Innervation of Intrafusal Muscle Fibers

Researchers developed a human-based in vitro muscle sensory circuit utilizing human stem cells. A serum-free medium was developed to drive the induction of intrafusal fibers from human satellite cells by actuation of a neuregulin signaling pathway. Both bag and chain intrafusal fibers were generated and subsequently validated by phase microscopy and immunocytochemistry. When co-cultured with proprioceptive sensory neurons derived from human neuroprogenitors, mechanosensory nerve terminal structural features with intrafusal fibers were demonstrated. [Biomaterials] Abstract

Autophagy Inhibition Overcomes Multiple Mechanisms of Resistance to BRAF Inhibition in Brain Tumors

Kinase inhibitors are effective cancer therapies, but tumors frequently develop resistance. Current strategies to circumvent resistance target the same or parallel pathways. Investigators report that targeting a completely different process, autophagy, can overcome multiple BRAF inhibitor resistance mechanisms in brain tumors. BRAF^V600Emutations occur in many pediatric brain tumors. [eLife] Full Article

Single-Cell Transcriptomic Analysis Defines Heterogeneity and Transcriptional Dynamics in the Adult Neural Stem Cell Lineage

Neural stem cells (NSCs) in the adult mammalian brain serve as a reservoir for the generation of new neurons, oligodendrocytes, and astrocytes. Scientists used single-cell RNA sequencing to characterize adult NSC populations and examine the molecular identities and heterogeneity of in vivo NSC populations. [Cell Rep] Full Article | Graphical Abstract

Primary Cell Culture of Live Neurosurgically Resected Aged Adult Human Brain Cells and Single Cell Transcriptomics

The authors developed a culturing system, based on a papain-aided procedure, for resected adult human brain tissue removed during neurosurgery. They performed single-cell transcriptomics on over 300 cells, permitting identification of oligodendrocytes, microglia, neurons, endothelial cells, and astrocytes after three weeks in culture. Using deep sequencing, they detected over 12,000 expressed genes, including hundreds of cell-type-enriched mRNAs, lncRNAs and pri-miRNAs. [Cell Rep] Full Article | Press Release | Graphical Abstract

Efficient CRISPR/Cas9-Assisted Gene Targeting Enables Rapid and Precise Genetic Manipulation of Mammalian Neural Stem Cells

Investigators deployed CRISPR/Cas technology to demonstrate a variety of sophisticated genetic modifications via gene targeting in both mouse and human neural stem cell lines, including: 1) efficient targeted transgene insertion at safe harbor loci (Rosa26 and AAVS1); 2) biallelic knockout of neurodevelopmental transcription factor genes; 3) simple knockin of epitope tags and fluorescent reporters; and 4) engineering of glioma mutations. [Development] Abstract | Full Article

The Clinically Approved Antiviral Drug Sofosbuvir Inhibits Zika Virus Replication

Scientists found that sofosbuvir inhibits Zika virus (ZIKV) RNA polymerase, targeting conserved amino acid residues. Sofosbuvir inhibited ZIKV replication in different cellular systems, such as hepatoma cells, neuroblastoma cells, neural stem cells and brain organoids. [Sci Rep] Full Article

Efficient Generation of hPSC-Derived Midbrain Dopaminergic Neurons in a Fully Defined, Scalable, 3D Biomaterial Platform

Researchers used a fully defined, 3D, thermoresponsive biomaterial platform to rapidly generate large numbers of action-potential firing midbrain dopaminergic (mDA) neurons after 25 days of differentiation. mDA neurons generated in 3D exhibited a 30-fold increase in viability upon implantation into rat striatum compared to neurons generated on 2D, consistent with the elevated expression of survival markers FOXA2 and EN1 in 3D. [Sci Rep] Full Article

PTEN: Local and Global Modulation of Neuronal Function in Health and Disease

The authors discuss how understanding the modulation of synaptic function by phosphatase and tensin homolog deleted on chromosome ten (PTEN) in Alzheimer’s disease and autism may contribute to the development of new therapies. [Trends Neurosci] Abstract

Understanding Parkinson’s Disease through the Use of Cell Reprogramming

The authors discuss the strategies that have been employed to generate ventral midbrain dopamine neurons and their potential for the study and treatment of Parkinson’s disease. [Stem Cell Rev] Abstract

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

Genervon Releases ALS, PD and AD Disease Associated Gene Lists Modulated by GM6 and Encourages Researchers to Explore New Discoveries beyond Single Target Drug Development Paradigm

Genervon Biopharmaceuticals LLC. has published a confidential list of genes associated with Parkinson’s disease. Genervon decided to share their confidential research findings, including the specific gene names, with the research communities with the goal of persuading neurological researchers to go beyond the single target drug development paradigm. [Press release from Genervon Biopharmaceuticals LLC. discussing research presented at the JP Morgan Healthcare Conference 2017, San Francisco] Press Release

Support for Chicago Biomedical Consortium Renewed

The Searle Funds at the Chicago Community Trust has renewed its funding commitment to the Chicago Biomedical Consortium, an innovative research and education collaboration of Northwestern University, the University of Illinois at Chicago and the University of Chicago that has helped establish the Chicago area as a leader in biomedical sciences. [Northwestern University] Press Release

Seqirus and Zambon Enter into a Partnership for Parkinson’s Disease Product in Australia and New Zealand

Newron Pharmaceuticals S.p.A. announced the news from its partner Zambon S.p.A., that it has entered into a long-term partnership with Seqirus covering Zambon’s Parkinson’s disease product (Xadago^®) in Australia and New Zealand. Zambon will be responsible for product supply and Seqirus will undertake registration and commercialisation of the product. [Newron Pharmaceuticals S.p.A. (Business Wire, Inc.)] Press Release

Tocagen Expands Toca 5, Phase II/III Clinical Trial for Recurrent Brain Cancer, to South Korea

Tocagen Inc. announced its randomized, controlled Phase II/III Clinical Trial, called Toca 5, is now enrolling patients in South Korea. The trial is ongoing in the United States, Canada and Israel. The study compares a cancer-selective virus, Toca 511 (vocimagene amiretrorepvec), in combination with Toca FC, to standard of care in patients with first or second recurrence of glioblastoma or anaplastic astrocytoma who are undergoing resection. [Tocagen Inc.] Press Release

U.S. Abandons Controversial Consent Proposal on Using Human Research Samples

Federal officials have dropped a controversial plan to impose new rules that researchers say would have made it much harder to use patient blood and tissue samples in research. The final Common Rule omits these provisions, but leaves other changes intact. [ScienceInsider] Editorial

Rigorous Replication Effort Succeeds for Just Two of Five Cancer Papers

The first results of a high-profile effort to replicate influential papers in cancer biology are roiling the biomedical community. Of the five studies the project has tackled so far, some involving experimental treatments already in clinical trials, only two could be repeated; one could not, and technical problems stymied the remaining two replication efforts. The Searle Funds has pledged $21 million over five years for initiatives that include a forum for academic and industry scientists to discuss commercialization ideas and a program supporting translational research projects with funding and early commercial guidance. [ScienceInsider] Editorial

NEW Gordon Research Conference – Glial Biology: Functional Interactions among Glia & Neurons
March 5-10, 2017
Ventura, California, United States

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

NEW Postdoctoral Researcher – Stem Cell Differentiation (University of Oklahoma)

NEW 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)

Postdoctoral Research Scholar – Neurodegenerative Diseases (Buck Insititute)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

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

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