Neural Cell News Volume 10.45 | Nov 16 2016

TOP STORY

In Vivo Genome Editing via CRISPR/Cas9 Mediated Homology-Independent Targeted Integration

Scientists devised a homology-independent targeted integration (HITI) strategy, which allows for robust DNA knock-in in both dividing and non-dividing cells in vitro and, more importantly, in vivo (for example, in neurons of postnatal mammals). As a proof of concept of its therapeutic potential, they demonstrated the efficacy of HITI in improving visual function using a rat model of the retinal degeneration condition retinitis pigmentosa. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

Qki Deficiency Maintains Stemness of Glioma Stem Cells in Suboptimal Environment by Downregulating Endolysosomal Degradation

Researchers discovered that Qki is a major regulator of neurals stem cell (NSC) stemness. Qk deletion on a Pten^−/−; Trp53^−/− background helps NSCs maintain their stemness outside the subventricular zone in Nes-CreER^T2; Qk^L/L; Pten^L/L; Trp53^L/L mice, which develop glioblastoma with a penetrance of 92% and a median survival time of 105 days. [Nat Genet] Abstract | Press Release

Capturing the Biology of Disease Severity in a PSC-Based Model of Familial Dysautonomia

Investigators presented disease-related phenotypes in human pluripotent stem cells (PSCs) that capture familial dysautonomia severity. Cells from individuals with severe but not mild disease show impaired specification of neural crest derivatives, including autonomic and sensory neurons. [Nat Med] Abstract

Enzymatic Activity of the Scaffold Protein Rapsyn for Synapse Formation

This study identifies a previously unappreciated enzymatic function of rapsyn and a role of neddylation in synapse formation, and reveals a potential target of therapeutic intervention for relevant neurological disorders. [Neuron] Abstract

Lack of Diaph3 Relaxes the Spindle Checkpoint Causing the Loss of Neural Progenitors

The authors report that Diaph3 is required before cell fission, to ensure the accurate segregation of chromosomes. Inactivation of the Diaph3 gene causes a massive loss of cortical progenitor cells, with subsequent depletion of intermediate progenitors and neurons, and results in microcephaly. [Nat Commun] Full Article

Sam68 Promotes Self-Renewal and Glycolytic Metabolism in Mouse Neural Progenitor Cells by Modulating Aldh1a3 Pre-mRNA 3′-End Processing

The balance between self-renewal and differentiation of neural progenitor cells (NPCs) dictates neurogenesis and proper brain development. Investigators found that the RNA binding protein Sam68 is strongly expressed in neurogenic areas of the neocortex and supports the self-renewing potential of mouse NPCs. Knockout of Sam68 constricted the pool of proliferating NPCs by accelerating their cell cycle exit and differentiation into post-mitotic neurons. [eLife] Abstract

FcγRIIb-SHIP2 Axis Links aβ to Tau Pathology by Disrupting Phosphoinositide Metabolism in Alzheimer’s Disease Model

The authors showed that the FcγRIIb-SHIP2 axis is critical in Aβ_1-42-induced tau pathology. Fcgr2b knockout or antagonistic FcγRIIb antibody inhibited Aβ_1-42-induced tau hyperphosphorylation and rescued memory impairments in Alzheimer’s disease (AD) mouse models. FcγRIIb phosphorylation at Tyr273 was found in AD brains, in neuronal cells exposed to Aβ_1-42, and recruited SHIP2 to form a protein complex. [eLife] Full Article

Macrophage Ontogeny underlies Differences in Tumor-Specific Education in Brain Malignancies

Scientists employed multiple models of murine brain malignancy and genetic lineage tracing to demonstrate that peripherally derived macrophages (BMDMs) are abundant in primary and metastatic brain tumors. They demonstrated that microglia specifically repress Itga4 (CD49D), enabling its utility as a discriminatory marker between microglia and BMDMs in primary and metastatic disease in mouse and human. [Cell Rep] Full Article | Graphical Abstract

CGG Repeat-Induced FMR1 Silencing Depends on the Expansion Size in Human iPSCs and Neurons Carrying Unmethylated Full Mutations

In fragile X syndrome, CGG repeat expansion greater than 200 triplets is believed to trigger FMR1 gene silencing and disease etiology. The authors showed that hypomethylation of the FMR1 promoter is maintained in induced pluripotent stem cells (iPSCs) derived from two unmethylated full mutation (UFM) individuals. However, a subset of iPSC clones with large CGG expansions carries silenced FMR1. They demonstrated de novo silencing upon expansion of the CGG repeat size. [Stem Cell Reports] Full Article | Graphical Abstract

Sex-Specific Effects of Testosterone on the Sexually Dimorphic Transcriptome and Epigenome of Embryonic Neural Stem/Progenitor Cells

Using a mouse embryonic neural stem cell model to understand early events contributing to sexually dimorphic brain development, researchers identified novel interactions between chromosomal sex and hormonal exposure that are instrumental to early brain sex differences. [Sci Rep] Full Article

Subarachnoid Hemorrhage Promotes Proliferation, Differentiation, and Migration of Neural Stem Cells via BDNF Upregulation

Researchers used a rat model of subarachnoid hemorrhage (SAH) to examine the extent of neurogenesis in the subventricular zone (SVZ) and assessed functional effects of the neurotrophic factors in the cerebrospinal fluid on neural stem cells (NSCs) after SAH. In this study, the proliferation, differentiation, and migratory capacities of NSCs in the SVZ were significantly increased on days five and seven post SAH. [PLoS One] Full Article

Network Abnormalities and Interneuron Dysfunction in Alzheimer Disease

Interneuron dysfunction and network abnormalities have emerged as potential mechanisms of cognitive dysfunction in Alzheimer’s disease and related disorders. The authors explore the concept that modulating these mechanisms may help to improve brain function in these conditions. [Nat Rev Neurosci] Abstract

Glioblastoma: Exosome and MicroRNA as Novel Diagnosis Biomarkers

The authors highlighted various exosomes and microRNAs that could be used for diagnosis and/or prognosis biomarkers in patients with glioblastoma. [Cancer Gene Ther] Abstract

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

Pitt Professor Receives $21.8 Million to Study Exercise/Brain-Health Link in Older Adults

Kirk Erickson, associate professor of psychology at the University of Pittsburgh, will conduct such a trial thanks to a five-year, $21.8 million grant from the National Institute on Aging. [University of Pittsburgh] Press Release

NIH Grants Emory $5.4M to Continue Work in Udall Parkinson’s Disease Research Center

Emory University will receive more than $1 million each year for the next five years from the NIH, renewing the NIH’s support for Emory’s Morris K. Udall Center of Excellence in Parkinson’s Disease Research. With a goal of developing more effective Parkinson’s disease treatments that have fewer side effects, the Emory Udall Center will integrate cutting-edge collaborative research, expert training of researchers and clinicians, and open dialogue with the general public. [Emory University] Press Release

Aptinyx Awarded up to $2.85 Million in NIH Grants to Research NMDA Receptor Modulation for the Treatment of Neuropathic Pain and AgeRelated Cognitive Decline

Aptinyx Inc. announced it has been awarded up to $2.85 million in research grants from divisions of the National Institutes of Health (NIH). [Aptinyx Inc.] Press Release

UCSF, Governor Brown Announce New Precision Medicine Projects

Continuing California’s groundbreaking effort to better treat and prevent diseases through advanced computing, Governor Edmund G. Brown Jr. and UC San Francisco announced six new projects have been selected for the California Initiative to Advance Precision Medicine. [University of California San Francisco] Press Release

FDA Funds UCSF-Stanford Center on Regulatory Science

The U.S. Food and Drug Administration (FDA) has awarded the UCSF-Stanford Center of Excellence in Regulatory Science and Innovation a five-year grant with up to $25 million in funding. UCSF-Stanford CERSI brings together a world-class team of scientists from two outstanding academic institutions, with partners at the FDA, to spur new approaches and technology to enhance the FDA’s ability to evaluate and approve new medical products. [University of California San Francisco] Press Release

In Bold New Step, Dutch Science Academy Holds Women-Only Elections

In order to reduce its perpetual gender imbalance—87% of its 556 members are men—the Royal Netherlands Academy of Arts and Sciences seeks to recruit ten new members in 2017 and six more in 2018, all with two X chromosomes. [ScienceInsider] Editorial

How Self-Appointed Guardians of “Sound Science” Tip the Scales Toward Industry

At a time when public mistrust of science runs high, and non-experts are hard-pressed to separate fact from industry-sponsored spin, Sense About Science, a charity based in London with an affiliate in New York, presents itself as a trustworthy arbiter. The organization purports to help the misinformed public sift through alarmist claims about public health and the environment by directing journalists, policymakers, and others to vetted sources who can explain the evidence behind debates about controversial products like e-cigarettes and flame retardants. [The Intercept_] Editorial

CRISPR Gene-Editing Tested in a Person for the First Time

A Chinese group has become the first to inject a person with cells that contain genes edited using the revolutionary CRISPR–Cas9 technique. A team led by oncologist Lu You at Sichuan University in Chengdu delivered the modified cells into a patient with aggressive lung cancer as part of a clinical trial at the West China Hospital, also in Chengdu. The move by Chinese scientists could spark a biomedical duel between China and the United States. [Nature News] Editorial

Embryonic Stem Cells and Fetal Tissue Research—Will Trump Intervene?

Of all the materials valued in biomedical research, embryonic stem (ES) cells and fetal tissue have gotten disproportionate attention from politicians. Because creating ES cell lines initially requires destroying a human embryo, President George W. Bush tightly restricted the use of federal funds for research on all but a few stem cell lines. President Barack Obama then made lifting those restrictions one of his first official actions after he took office in 2009. [Science Insider] Editorial

NEW Gordon Research Conference: Stem Cells & Cancer
February 12-17, 2017
Barga, Italy

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

NEW Neuroscience Postdoctoral Fellow (Harvard University)

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

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

Computational Biologist – Aging Brain (Columbia University)

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

NYSCF Investigator – Stem Cell And Neuroscience (New York Stem Cell Foundation)

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)

Assistant Professor (Tenure) – Developmental Biology)

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