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https://www.readbyqxmd.com/read/29149419/changes-in-chromatin-state-reveal-arnt2-at-a-node-of-a-tumorigenic-transcription-factor-signature-driving-glioblastoma-cell-aggressiveness
#1
Alexandra Bogeas, Ghislaine Morvan-Dubois, Elias A El-Habr, François-Xavier Lejeune, Matthieu Defrance, Ashwin Narayanan, Klaudia Kuranda, Fanny Burel-Vandenbos, Salwa Sayd, Virgile Delaunay, Luiz G Dubois, Hugues Parrinello, Stéphanie Rialle, Sylvie Fabrega, Ahmed Idbaih, Jacques Haiech, Ivan Bièche, Thierry Virolle, Michele Goodhardt, Hervé Chneiweiss, Marie-Pierre Junier
Although a growing body of evidence indicates that phenotypic plasticity exhibited by glioblastoma cells plays a central role in tumor development and post-therapy recurrence, the master drivers of their aggressiveness remain elusive. Here we mapped the changes in active (H3K4me3) and repressive (H3K27me3) histone modifications accompanying the repression of glioblastoma stem-like cells tumorigenicity. Genes with changing histone marks delineated a network of transcription factors related to cancerous behavior, stem state, and neural development, highlighting a previously unsuspected association between repression of ARNT2 and loss of cell tumorigenicity...
November 17, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/29141672/a-novel-git2-braf-fusion-in-pilocytic-astrocytoma
#2
Jeffrey Helgager, Hart G Lidov, Navin R Mahadevan, Mark W Kieran, Keith L Ligon, Sanda Alexandrescu
BACKGROUND: KIAA1549-BRAF fusion is the most common genetic event in pilocytic astrocytoma (PA), and leads to activation of the mitogen activated protein kinase (MAPK) signaling pathway. Fusions of BRAF with other partner genes, as well as other genetic alterations not involving BRAF but also leading to MAPK pathway activation have been described rarely. CASE PRESENTATION: We present a new fusion partner in the low-grade glioma of a 10-year-old male, who presented with headaches and recent episodes of seizures...
November 15, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/29133394/role-of-estrogen-receptor-beta-in-neural-differentiation-of-mouse-embryonic-stem-cells
#3
Mukesh K Varshney, José Inzunza, Diana Lupu, Vaidheeswaran Ganapathy, Per Antonson, Joëlle Rüegg, Ivan Nalvarte, Jan-Åke Gustafsson
The ability to propagate mature cells and tissue from pluripotent stem cells offers enormous promise for treating many diseases, including neurodegenerative diseases. Before such cells can be used successfully in neurodegenerative diseases without causing unwanted cell growth and migration, genes regulating growth and migration of neural stem cells need to be well characterized. Estrogen receptor beta (ERβ) is essential for migration of neurons and glial cells in the developing mouse brain. To examine whether ERβ influences differentiation of mouse embryonic stem cells (mESC) into neural lineages, we compared control and ERβ knockout (BERKO) mESCs at defined stages of neural development and examined the effects of an ERβ-selective ligand (LY3201) with a combination of global and targeted gene-expression profiling and the expression of key pluripotency markers...
November 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29122585/strong-sonic-hedgehog-signaling-in-the-mouse-ventral-spinal-cord-is-not-required-for-oligodendrocyte-precursor-cell-opc-generation-but-is-necessary-for-correct-timing-of-its-generation
#4
Hirokazu Hashimoto, Wen Jiang, Takeshi Yoshimura, Kyeong-Hye Moon, Jinwoong Bok, Kazuhiro Ikenaka
In the mouse neural tube, sonic hedgehog (Shh) secreted from the floor plate (FP) and the notochord (NC) regulates ventral patterning of the neural tube, and later is essential for the generation of oligodendrocyte precursor cells (OPCs). During early development, the NC is adjacent to the neural tube and induces ventral domains in it, including the FP. In the later stage of development, during gliogenesis in the spinal cord, the pMN domain receives strong Shh signaling input. While this is considered to be essential for the generation of OPCs, the actual role of this strong input in OPC generation remains unclear...
November 6, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/29111096/multinodular-and-vacuolating-neuronal-tumor-of-the-cerebrum-a-rare-entity-new-case-and-review-of-the-literature
#5
Lain Hermes Gonzalez-Quarante, Fernando Ruiz-Juretschke, Emma Sola Vendrell, Oscar Lucas Gil de Sagredo Del Corral, Vijay Agarwal, Roberto Garcia-Leal
BACKGROUND: Multinodular and vacuolating neuronal tumor has been recently described and included in the World Health Organization Classification of Tumors of The Central Nervous System, even though its consideration as a true tumor is controversial. Patients with these lesions usually present with refractory seizures and inconclusive imaging findings that may be confused with other more common diagnoses such as dysembryoplastic neuroepithelial tumors or low-grade gliomas. Therefore, surgical resection is warranted to reach a pathologic diagnosis and seizure control...
October 28, 2017: Neurocirugía
https://www.readbyqxmd.com/read/29107533/h3-3-k27m-cooperates-with-trp53-loss-and-pdgfra-gain-in-mouse-embryonic-neural-progenitor-cells-to-induce-invasive-high-grade-gliomas
#6
Manav Pathania, Nicolas De Jay, Nicola Maestro, Ashot S Harutyunyan, Justyna Nitarska, Pirasteh Pahlavan, Stephen Henderson, Leonie G Mikael, Angela Richard-Londt, Ying Zhang, Joana R Costa, Steven Hébert, Sima Khazaei, Nisreen Samir Ibrahim, Javier Herrero, Antonella Riccio, Steffen Albrecht, Robin Ketteler, Sebastian Brandner, Claudia L Kleinman, Nada Jabado, Paolo Salomoni
Gain-of-function mutations in histone 3 (H3) variants are found in a substantial proportion of pediatric high-grade gliomas (pHGG), often in association with TP53 loss and platelet-derived growth factor receptor alpha (PDGFRA) amplification. Here, we describe a somatic mouse model wherein H3.3(K27M) and Trp53 loss alone are sufficient for neoplastic transformation if introduced in utero. H3.3(K27M)-driven lesions are clonal, H3K27me3 depleted, Olig2 positive, highly proliferative, and diffusely spreading, thus recapitulating hallmark molecular and histopathological features of pHGG...
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29081882/derivation-of-telencephalic-oligodendrocyte-progenitors-from-human-pluripotent-stem-cells
#7
Tamara Major, Ann Powers, Viviane Tabar
Oligodendrocytes are the main myelinating cell of the adult CNS and are vulnerable to injury in diverse disorders such as spinal cord injury, stroke, trauma, pharmacological and radiation toxicity, as well as neuroinflammation. Human pluripotent stem cells are attractive sources of oligodendrocyte lineage cells and provide a promising treatment strategy for exogenous myelin repair through transplantation. This unit describes a protocol for the step-wise differentiation of forebrain late oligodendrocyte progenitor cells (OPCs) from human pluripotent stem cells in defined chemical in vitro culture conditions...
November 8, 2017: Current Protocols in Stem Cell Biology
https://www.readbyqxmd.com/read/29079486/exposure-to-fine-and-ultrafine-particulate-matter-during-gestation-alters-postnatal-oligodendrocyte-maturation-proliferation-capacity-and-myelination
#8
Carolyn Klocke, Joshua L Allen, Marissa Sobolewski, Jason L Blum, Judith T Zelikoff, Deborah A Cory-Slechta
Accumulating studies indicate that the brain is a direct target of air pollution exposure during the fetal period. We have previously demonstrated that exposure to concentrated ambient particles (CAPs) during gestation produces ventriculomegaly, periventricular hypermyelination, and enlargement of the corpus callosum (CC) during postnatal development in mice. This study aimed to further characterize the cellular basis of the observed hypermyelination and determine if this outcome, among other effects, persisted as the brain matured...
October 24, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/29076551/tgf-%C3%AE-pro-oligodendrogenic-effects-on-adult-svz-progenitor-cultures-and-its-interaction-with-the-notch-signaling-pathway
#9
Laura I Gómez Pinto, Debora Rodríguez, Ana M Adamo, Patricia A Mathieu
Adult neural progenitor cells (NPCs) are capable of differentiating into neurons, astrocytes, and oligodendrocytes throughout life. Notch and transforming growth factor β1 (TGF-β) signaling pathways play critical roles in controlling these cell fate decisions. TGF-β has been previously shown to exert pro-neurogenic effects on hippocampal and subventricular zone (SVZ) NPCs in vitro and to interact with Notch in different cellular types. Therefore, the aim of our work was to study the effect of TGF-β on adult rat brain SVZ NPC glial commitment and its interaction with Notch signaling...
October 27, 2017: Glia
https://www.readbyqxmd.com/read/29074702/respiratory-consequences-of-targeted-losses-of-hoxa5-gene-function-in-mice
#10
Kim Landry-Truchon, Stéphanie Fournier, Nicolas Houde, Jean-Philippe Rousseau, Lucie Jeannotte, Richard Kinkead
Fetal development of the respiratory tract and diaphragm requires strict coordination between genetically controlled signals and mechanical forces produced by the neural network that generates breathing. Being expressed in the mesenchyme of trachea, lung and diaphragm, and in phrenic motoneurons HOXA5 is a key transcription factor regulating lung development and function. Consequently, most Hoxa5(-/-) mutants die at birth from respiratory failure. However, the extensive effect of the null mutation makes it difficult to identify the origins of respiratory dysfunction in newborns...
October 26, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/29071135/grifolin-attenuates-white-matter-lesion-in-oxygen-glucose-deprivation
#11
Ying Yanqin, Tang Jing, Chen Wei, Li Nan
The present study evaluates the effect of grifolin (GFL) in oxygen/glucose deprivation (OGD) induced white matter lesion. Injury induced with OGD was found to be significant at the 9th h of OGD induction and the effect of GFL on the proliferation of oligodendrocyte precursor cells (OPCs) was assessed by CCK-8 and Hoechst 33258 assay at GFL 1, 5, 25, 50 and 100 μm concentrations. Whereas immunocytochemistry was performed for the assessment of survival and apoptosis of OPCs, western blot assay and RT-PCR were performed after 8th day of OGD injury for the estimation of expressions of myelin basic protein (MBP) and inhibitor of DNA binding 2 (Id2) in OPCs respectively...
2017: Translational Neuroscience
https://www.readbyqxmd.com/read/29049317/identification-of-genome-wide-targets-of-olig2-in-the-adult-mouse-spinal-cord-using-chip-seq
#12
Andrew J Darr, Matt C Danzi, Lee Brady, Dorothea Emig-Agius, Amber Hackett, Roozbeh Golshani, Nikita Warner, Jae Lee, Vance P Lemmon, Pantelis Tsoulfas
In jawed vertebrates, oligodendrocytes (OLs) are the myelin-producing glial cells responsible for ensheathment of axons within the central nervous system and are also crucial for remyelination following injury or disease. Olig2 is a crucial factor in the specification and differentiation of oligodendrocyte precursor cells (OPCs) that give rise to mature, myelin-producing OLs in the developing and postnatal CNS; however, its role in adulthood is less well understood. To investigate the role Olig2 plays in regulating gene expression in the adult OL lineage in a physiologically-relevant context, we performed chromatin immunoprecipitation followed by next generation sequencing analysis (ChIP-Seq) using whole spinal cord tissue harvested from adult mice...
2017: PloS One
https://www.readbyqxmd.com/read/29034508/ulk4-deficiency-leads-to-hypomyelination-in-mice
#13
Min Liu, Ping Xu, Zhenlong Guan, Xiaohong Qian, Peter Dockery, Una Fitzgerald, Timothy O'Brien, Sanbing Shen
Brain nerve fibers are insulated by myelin which is produced by oligodendrocytes. Defects in myelination are increasingly recognized as a common pathology underlying neuropsychiatric and neurodevelopmental disorders, which are associated with deletions of the Unc-51-like kinase 4 (ULK4) gene. Key transcription factors have been identified for oligodendrogenesis, but little is known about their associated regulators. Here we report that Ulk4 acts as a key regulator of myelination. Myelination is reduced by half in the Ulk4(tm1a/tm1a) hypomorph brain, whereas expression of axonal marker genes Tubb3, Nefh, Nefl and Nefm remains unaltered...
January 2018: Glia
https://www.readbyqxmd.com/read/29027701/cellular-and-molecular-characterization-of-idh1-mutated-diffuse-low-grade-gliomas-reveals-tumor-heterogeneity-and-absence-of-egfr-pdgfr%C3%AE-activation
#14
S Azar, N Leventoux, C Ripoll, V Rigau, C Gozé, F Lorcy, L Bauchet, H Duffau, P O Guichet, B Rothhut, J P Hugnot
Diffuse low grade gliomas (DLGG, grade II gliomas) are slowly-growing brain tumors that often progress into high grade gliomas. Most tumors have a missense mutation for IDH1 combined with 1p19q codeletion in oligodendrogliomas or ATRX/TP53 mutations in astrocytomas. The phenotype of tumoral cells, their environment and the pathways activated in these tumors are still ill-defined and are mainly based on genomics and transcriptomics analysis. Here we used freshly-resected tumors to accurately characterize the tumoral cell population and their environment...
October 13, 2017: Glia
https://www.readbyqxmd.com/read/28990708/astroblastoma-a-distinct-tumor-entity-characterized-by-alterations-of-the-x-chromosome-and-mn1-rearrangement
#15
Takanori Hirose, Sumihito Nobusawa, Kazuhiko Sugiyama, Vishwa J Amatya, Naomi Fujimoto, Atsushi Sasaki, Yoshiki Mikami, Akiyoshi Kakita, Shinya Tanaka, Hideaki Yokoo
Astroblastoma is a rare, enigmatic tumor of the central nervous system (CNS) which shares some clinicopathologic aspects with other CNS tumors, especially ependymoma. To further clarify the nature of astroblastoma, we performed clinicopathologic and molecular genetic studies on eight cases of astroblastoma. The median age of the patients was 14.5 years, ranging from 5 to 60 years, and seven of the patients were female. All tumors arose in the cerebral hemisphere and radiologically appeared to be well-bordered, nodular tumors often associated with cystic areas and contrast-enhancement...
October 9, 2017: Brain Pathology
https://www.readbyqxmd.com/read/28989170/olig2-silence-ameliorates-cuprizone-induced-schizophrenia-like-symptoms-in-mice
#16
Hongxia Liu, Jinguo Zhai, Bin Wang, Maosheng Fang
BACKGROUND The pathogenesis of schizophrenia is complex and oligodendrocyte abnormality is an important component of the pathogenesis found in schizophrenia. This study was designed to evaluate the function of olig2 in cuprizone-induced schizophrenia-like symptoms in a mouse model, and to assess the related mechanisms. MATERIAL AND METHODS The schizophrenia-like symptoms were modeled by administration of cuprizone in mice. Open-field and elevated-plus maze tests were applied to detect behavioral changes. Adenovirus encoding olig2 siRNA was designed to silence olig2 expression...
October 9, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28987163/cellular-reactions-of-the-central-nervous-system
#17
Gabor G Kovacs
Major cell types of the central nervous system comprise neurons, glial cells (astrocytes, oligodendrocytes, ependymal cells, and microglia), choroid plexus cells, cells related to blood vessels and coverings. These cells show a wide range of reactions to various noxious agents, which can be detected in routine stainings. Some of these reactions are nonspecific to different injuries; however some, such as the appearance of inclusion bodies, can be highly disease-specific. Immunohistochemical markers are widely used in neuropathologic diagnostic practice and help to understand the pathogenesis of diseases...
2017: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/28934247/the-extent-of-intrauterine-growth-restriction-determines-the-severity-of-cerebral-injury-and-neurobehavioural-deficits-in-rodents
#18
Crystal A Ruff, Stuart D Faulkner, Prakasham Rumajogee, Stephanie Beldick, Warren Foltz, Jennifer Corrigan, Alfred Basilious, Shangjun Jiang, Shanojan Thiyagalingam, Jerome Y Yager, Michael G Fehlings
BACKGROUND: Cerebral Palsy (CP) is the most common physical pediatric neurodevelopmental disorder and spastic diplegic injury is its most frequent subtype. CP results in substantial neuromotor and cognitive impairments that have significant socioeconomic impact. Despite this, its underlying pathophysiological mechanisms and etiology remain incompletely understood. Furthermore, there is a need for clinically relevant injury models, which a) reflect the heterogeneity of the condition and b) can be used to evaluate new translational therapies...
2017: PloS One
https://www.readbyqxmd.com/read/28925404/ing5-activity-in-self-renewal-of-glioblastoma-stem-cells-via-calcium-and-follicle-stimulating-hormone-pathways
#19
F Wang, A Y Wang, C Chesnelong, Y Yang, A Nabbi, S Thalappilly, V Alekseev, K Riabowol
Stem cell-like brain tumor initiating cells (BTICs) cause recurrence of glioblastomas, with BTIC 'stemness' affected by epigenetic mechanisms. The ING family of epigenetic regulators (ING1-5) function by targeting histone acetyltransferase (HAT) or histone deacetylase complexes to the H3K4me3 mark to alter histone acetylation and subsequently, gene expression. Here we find that ectopic expression of ING5, the targeting subunit of HBO1, MOZ and MORF HAT complexes increases expression of the Oct4, Olig2 and Nestin stem cell markers, promotes self-renewal, prevents lineage differentiation and increases stem cell pools in BTIC populations...
September 18, 2017: Oncogene
https://www.readbyqxmd.com/read/28925399/dock4-promotes-loss-of-proliferation-in-glioblastoma-progenitor-cells-through-nuclear-beta-catenin-accumulation-and-subsequent-mir-302-367-cluster-expression
#20
D N Debruyne, L Turchi, F Burel-Vandenbos, M Fareh, F Almairac, V Virolle, D Figarella-Branger, N Baeza-Kallee, P Lagadec, V Kubiniek, P Paquis, D Fontaine, M-P Junier, H Chneiweiss, T Virolle
Glioblastomas (GBM) are lethal primitive brain tumours characterized by a strong intra-tumour heterogeneity. We observed in GBM tissues the coexistence of functionally divergent micro-territories either enriched in more differentiated and non-mitotic cells or in mitotic undifferentiated OLIG2 positive cells while sharing similar genomic abnormalities. Understanding the formation of such functionally divergent micro-territories in glioblastomas (GBM) is essential to comprehend GBM biogenesis, plasticity and to develop therapies...
September 18, 2017: Oncogene
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