Neural Cell News Volume 10.43 | Nov 2 2016

TOP STORY

Single-Cell RNA-Seq Supports a Developmental Hierarchy in Human Oligodendroglioma

Investigators profiled 4,347 single cells from six IDH1 or IDH2 mutant human oligodendrogliomas by RNA sequencing (RNA-seq) and reconstruct their developmental programs from genome-wide expression signatures. The authors infer that most cancer cells are differentiated along two specialized glial programs, whereas a rare subpopulation of cells is undifferentiated and associated with a neural stem cell expression program. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

A Single-Cell Roadmap of Lineage Bifurcation in Human ESC Models of Embryonic Brain Development

Scientists integrated single-cell RNA sequencing and clonal analyses to reveal lineage trees and molecular signals underlying early forebrain and mid/hindbrain cell differentiation from human embryonic stem cells (ESCs). [Cell Stem Cell] Abstract | Press Release | Graphical Abstract

Predictive Markers Guide Differentiation to Improve Graft Outcome in Clinical Translation of hESC-Based Therapy for Parkinson’s Disease

Researchers took an unbiased approach to identify predictive markers expressed in dopamine neuron progenitors that correlate with graft outcome in an animal model of Parkinson’s disease through gene expression analysis of >30 batches of grafted human embryonic stem cell (hESC)-derived progenitors. [Cell Stem Cell] Full Article | Graphical Abstract

A Viral Strategy for Targeting and Manipulating Interneurons Across Vertebrate Species

Scientists describe a novel recombinant adeno-associated virus that restricts gene expression to GABAergic interneurons within the telencephalon. They demonstrated that the viral expression is specific and robust, allowing for morphological visualization, activity monitoring and functional manipulation of interneurons in both mice and non-genetically tractable species, thus opening the possibility to study GABAergic function in virtually any vertebrate species. [Nat Neurosci] Abstract

Polymer Thin Films with Tunable Acetylcholine-Like Functionality Enable Long-Term Culture of Primary Hippocampal Neurons

Scientists found that a polymer thin film with optimal acetylcholine-like functionality enables a long-term culture and survival of primary neurons. [ACS Nano] Abstract | Graphical Abstract

Coupling Optogenetic Stimulation with NanoLuc-Based Luminescence (BRET) Ca⁺⁺ Sensing

Scientists developed a genetically encoded Ca⁺⁺ sensor that is ratiometric by virtue of bioluminescence resonance energy transfer (BRET). Ca⁺⁺ fluxes that are elicited by brief pulses of light to cultured cells expressing melanopsin and to neurons-expressing channelrhodopsin are quantified and imaged with the BRET Ca⁺⁺ sensor in darkness, thereby avoiding undesirable consequences of fluorescence irradiation. [Nat Commun] Full Article | Press Release

Loss of Uhrf1 in Neural Stem Cells Leads to Activation of Retroviral Elements and Delayed Neurodegeneration

In order to understand whether early epigenetic mechanisms instruct the long-term behavior of neural stem cells (NSCs) and their progeny, investigators examined Uhrf1 (ubiquitin-like PHD ring finger-1; also known as Np95), as it is highly expressed in NSCs of the developing brain and rapidly down-regulated upon differentiation. [Genes Dev] Full Article | Press Release

Jointly Reduced Inhibition and Excitation Underlies Circuit-Wide Changes in Cortical Processing in Rett Syndrome

By whole-cell recording of synaptic responses in methyl-CpG binding protein 2 mutant mice in vivo, researchers showed that visually driven excitatory and inhibitory conductances are both reduced in cortical pyramidal neurons. [Proc Natl Acad Sci USA] Abstract

Vulnerability of Purkinje Cells Generated from Spinocerebellar Ataxia Type 6 Patient-Derived iPSCs

The authors succeeded in generating differentiated Purkinje cells that carry patient genes by combining disease-specific iPSCs and self-organizing culture technologies. Patient-derived Purkinje cells exhibit increased levels of full-length Cav2.1 protein but decreased levels of its C-terminal fragment and downregulation of the transcriptional targets TAF1 and BTG1. [Cell Rep] Full Article | Press Release | Graphical Abstract

Small Molecules Modulate Chromatin Accessibility to Promote NEUROG2-Mediated Fibroblast-to-Neuron Reprogramming

Pro-neural transcription factors and small molecules can induce the reprogramming of fibroblasts into functional neurons; however, the immediate-early molecular events that catalyze this conversion have not been well defined. Researchers demonstrated that neurogenin 2 (NEUROG2) is a pioneer factor, forskolin dorsomorphin enhances chromatin accessibility and H3K27 acetylation, and synergistic transcription activated by these factors is essential to successful reprogramming. [Stem Cell Reports] Full Article | Graphical Abstract

High-Throughput Toxicity and Phenotypic Screening of 3D Human Neural Progenitor Cell Cultures on a Microarray Chip Platform

Investigators used a 3D cell culture chip for high-throughput screening of a human neural progenitor (NPC) cell line. The differential toxicity of 24 compounds was determined on undifferentiated and differentiating NPCs. Five compounds led to significant differences in IC₅₀ values between undifferentiated and differentiating cultures. [Stem Cell Reports] Full Article | Graphical Abstract

Analysis of Induced Pluripotent Stem Cells Carrying 22q11.2 Deletion

The authors established human-induced pluripotent stem cells from two schizophrenia patients with the 22q11.2 deletion (two cell lines from each subject, total of four cell lines) and three controls (total of four cell lines). Neurosphere size, neural differentiation efficiency, neurite outgrowth, cellular migration and the neurogenic-to-gliogenic competence ratio were significantly reduced in patient-derived cells. [Transl Psychiatry] Full Article | Press Release

The Promises and Challenges of Human Brain Organoids as Models of Neuropsychiatric Disease

The authors discuss the advantages, limitations and future applications of human brain organoids as in vitro models of neuropsychiatric disease. [Nat Med] Full Article

Advances in Markers of Prodromal Parkinson Disease

Early Parkinson’s disease (PD) can be divided into preclinical, prodromal and clinical stages; the authors focus on the prodromal stage and markers that can be used to identify prodromal PD. [Nat Rev Neurol] Full Article

Glioblastoma, Hypoxia and Autophagy: A Survival-Prone ‘Ménage-à-Trois’

The authors summarize the most recent data about induction of autophagy under hypoxic condition and the role of autophagy in glioblastoma. [Cell Death Dis] Full Article

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

Over Half a Billion in Research Council Grant to Karolinska Institute (KI) Researchers

The Swedish Research Council announced the grants it will be awarding in the category of medicine and health. The total sum is almost 980 million Swedish krona (SEK), of which KI researchers will receive SEK 524,325,017. [Karolinska Institute] Press Release

Pioneering Drug Discovery Company Bridge Medicines Launched to Advance Promising Early Technologies in Major Academic Institutions through Human Proof of Concept

Memorial Sloan Kettering Cancer Center, The Rockefeller University and Weill Cornell Medicine announced that they have established a new drug discovery company called Bridge Medicines. Bridge Medicines is a groundbreaking initiative that completes a seamless, fully funded and professionally staffed path from concept to drug candidate to efficiently and rapidly develop innovative therapeutics for treating human diseases. [Memorial Sloan Kettering Cancer Center] Press Release

Novogen Asset Acquisition Acquires Mid-Stage Cancer Drug from Genentech

Novogen has in-licensed global rights to the Phase II-ready drug GDC-0084 from Genentech. GDC-0084 is designed to treat brain cancers, including the rapidly fatal glioblastoma (GBM). Novogen plans to initiate a Phase II trial in GBM next year and positive trial results could allow filing for accelerated approval in 2020. [Novogen] Press Release

Publisher Pulls 58 Articles by Iranian Scientists over Authorship Manipulation

A tranche of 58 articles authored by 282 Iran-based researchers were retracted by a leading scientific publisher, which said it had found signs that the peer review and publication processes had been compromised. [Nature News] Editorial

Young Scientists Ditch Postdocs for Biotech Start-Ups

There is a vanguard of young biomedical scientists who have started companies instead of taking the conventional academic path and pursuing postdoctoral studies after their PhDs. Among the factors driving this change are an infusion of money into early-stage biotech investing, the emergence of biotech incubators and the scarcity of academic jobs in science. [Nature News] Editorial

Beyond Trump vs Clinton: A Scientist’s Guide to the US Election

Choices that voters make will influence other levels of government — and some of these decisions will steer the course of science and science policy. [Nature News] Editorial

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January 27-30, 2017
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NEW Computational Biologist – Aging Brain (Columbia University)

Postdoctoral Fellow – Parkinson’s Disease Research (Van Andel Research Institute)

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Cancer Research – PhD Studentships (University of Cambridge)

Postdoctoral Fellow – Neural Stem/Progenitor Cells (University of California – San Francisco)

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

Assistant Professor – Neural Mechanisms of Motor Control (University of California – Davis)

Postdoctoral Researcher – iPS & ESC Parkinson’s Disease (VIB)

Postdoctoral Researcher – Neural Basis of Brain States (Ecole Polytechnique Fédérale de Lausanne)

Systems Neuroscientist (University of Rochester)

PhD – Neural Circuits (The International Max Planck Research School for Neural Circuits)

International PhD Studentships (Medical Research Council)

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