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https://www.readbyqxmd.com/read/28344151/enhancing-oligodendrocyte-differentiation-by-transient-transcription-activation-via-dna-nanoparticle-mediated-transfection
#1
Xiaowei Li, Stephany Y Tzeng, Camila Gadens Zamboni, Vassilis E Koliatsos, Guo-Li Ming, Jordan J Green, Hai-Quan Mao
Current approaches to derive oligodendrocytes from human pluripotent stem cells (hPSCs) need extended exposure of hPSCs to growth factors and small molecules, which limits their clinical application because of the lengthy culture time required and low generation efficiency of myelinating oligodendrocytes. Compared to extrinsic growth factors and molecules, oligodendrocyte differentiation and maturation can be more effectively modulated by regulation of the cell transcription network. In the developing central nervous system (CNS), two basic helix-loop-helix transcription factors, Olig1 and Olig2, are decisive in oligodendrocyte differentiation and maturation...
March 23, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28339768/the-transcription-factor-olig2-is-important-for-the-biology-of-diffuse-intrinsic-pontine-gliomas
#2
Jane L Anderson, Ranjithmenon Muraleedharan, Nicole Oatman, Amanda Klotter, Satarupa Sengupta, Ronald R Waclaw, Jianqiang Wu, Rachid Drissi, Lili Miles, Eric H Raabe, Matthew L Weirauch, Maryam Fouladi, Lionel M Chow, Lindsey Hoffman, Mariko DeWire, Biplab Dasgupta
Background.: Diffuse intrinsic pontine glioma (DIPG) is a high-grade brainstem glioma of children with dismal prognosis. There is no single unifying model about the cell of origin of DIPGs. Proliferating cells in the developing human and mouse pons, the site of DIPGs, express neural stem/progenitor cell (NPC) markers, including Sox2, nestin, vimentin, Olig2, and glial fibrillary acidic protein, in an overlapping and non-overlapping manner, suggesting progenitor cell heterogeneity in the pons...
February 23, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28328117/noonan-syndrome-ptpn11-mutations-and-brain-tumors-a-clinical-report-and-review-of-the-literature
#3
Aurore Siegfried, Claude Cances, Marie Denuelle, Najat Loukh, Maïté Tauber, Hélène Cavé, Marie-Bernadette Delisle
Noonan syndrome (NS), an autosomal dominant disorder, is characterized by short stature, congenital heart defects, developmental delay, and facial dysmorphism. PTPN11 mutations are the most common cause of NS. PTPN11 encodes a non-receptor protein tyrosine phosphatase, SHP2. Hematopoietic malignancies and solid tumors are associated with NS. Among solid tumors, brain tumors have been described in children and young adults but remain rather rare. We report a 16-year-old boy with PTPN11-related NS who, at the age of 12, was incidentally found to have a left temporal lobe brain tumor and a cystic lesion in the right thalamus...
April 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28326060/microbial-neuraminidase-induces-a-moderate-and-transient-myelin-vacuolation-independent-of-complement-system-activation
#4
Pablo Granados-Durán, María Dolores López-Ávalos, Manuel Cifuentes, Margarita Pérez-Martín, María Del Mar Fernández-Arjona, Timothy R Hughes, Krista Johnson, B Paul Morgan, Pedro Fernández-Llebrez, Jesús M Grondona
AIMS: Some central nervous system pathogens express neuraminidase (NA) on their surfaces. In the rat brain, a single intracerebroventricular (ICV) injection of NA induces myelin vacuolation in axonal tracts. Here, we explore the nature, the time course, and the role of the complement system in this damage. METHODS: The spatiotemporal analysis of myelin vacuolation was performed by optical and electron microscopy. Myelin basic protein-positive area and oligodendrocyte transcription factor (Olig2)-positive cells were quantified in the damaged bundles...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28293728/oligodendrocyte-precursor-cells-in-the-mouse-optic-nerve-originate-in-the-preoptic-area
#5
Katsuhiko Ono, Kengo Yoshii, Hiroyuki Tominaga, Hitoshi Gotoh, Tadashi Nomura, Hirohide Takebayashi, Kazuhiro Ikenaka
The present study aims to examine the origin of oligodendrocyte progenitor cells (OPCs) in the mouse optic nerve (ON) by labeling OPCs in the fetal forebrain. The labeling of OPCs in the ON was performed by injection of a retrovirus vector carrying the lacZ gene into the lateral ventricle, or by inducible Cre/loxP of Olig2-positive cells. The retrovirus labeling revealed that ventricular zone-derived cells of the fetal forebrain relocated to the ON and differentiated into oligodendrocytes. In addition, lineage tracing of Olig2-positive cells and whole-mount staining of PDGFRα-positive cells demonstrated that OPCs appeared by E12...
March 14, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28261150/intranasal-administration-of-the-antisecretory-peptide-af-16-reduces-edema-and-improves-cognitive-function-following-diffuse-traumatic-brain-injury-in-the-rat
#6
Fredrik Clausen, Hans-Arne Hansson, Johan Raud, Niklas Marklund
A synthetic peptide with antisecretory activity, antisecretory factor (AF)-16, improves injury-related deficits in water and ion transport and decreases intracranial pressure after experimental cold lesion injury and encephalitis although its role in traumatic brain injury (TBI) is unknown. AF-16 or an inactive reference peptide was administrated intranasally 30 min following midline fluid percussion injury (mFPI; n = 52), a model of diffuse mild-moderate TBI in rats. Sham-injured (n = 14) or naïve (n = 24) animals were used as controls...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28255270/activated-clc-2-inhibits-p-akt-to-repress-myelination-in-gdm-newborn-rats
#7
Feixiang He, Yuchen Peng, Zhi Yang, Zilu Ge, Yanping Tian, Teng Ma, Hongli Li
This study aims to investigate the effect and mechanism of type 2 voltage-gated chloride channel (ClC-2) on myelin development of newborn rats' cerebral white matter with gestational diabetes mellitus (GDM). In this study, GDM model was induced in late pregnant rat model. The alteration of ClC-2 expression in various developmental stages of cerebral white matter with/without being exposed to high glucose was analyzed using RT-PCR, active oxygen detection, TUNEL staining, Western Blot as well as immuno-histochemical staining...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28253550/olig1-is-required-for-noggin-induced-neonatal-myelin-repair
#8
Jennifer K Sabo, Vivi Heine, John C Silbereis, Lucas Schirmer, Steven W Levison, David H Rowitch
Objective - Neonatal white matter injury (NWMI) is a lesion found in preterm infants that can lead to cerebral palsy. Although antagonists of bone morphogenetic protein (BMP) signaling, such as Noggin, promote oligodendrocyte precursor cell (OPC) production after hypoxic-ischemic injury, the downstream functional targets are poorly understood. The bHLH protein Olig1 promotes oligodendrocyte (OL) development and is essential during remyelination in adult mice. Here, we investigated whether Olig1 function is required downstream of BMP antagonism for the response to injury in the neonatal brain...
March 2, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28246330/rapid-and-efficient-generation-of-oligodendrocytes-from-human-induced-pluripotent-stem-cells-using-transcription-factors
#9
Marc Ehrlich, Sabah Mozafari, Michael Glatza, Laura Starost, Sergiy Velychko, Anna-Lena Hallmann, Qiao-Ling Cui, Axel Schambach, Kee-Pyo Kim, Corinne Bachelin, Antoine Marteyn, Gunnar Hargus, Radia Marie Johnson, Jack Antel, Jared Sterneckert, Holm Zaehres, Hans R Schöler, Anne Baron-Van Evercooren, Tanja Kuhlmann
Rapid and efficient protocols to generate oligodendrocytes (OL) from human induced pluripotent stem cells (iPSC) are currently lacking, but may be a key technology to understand the biology of myelin diseases and to develop treatments for such disorders. Here, we demonstrate that the induction of three transcription factors (SOX10, OLIG2, NKX6.2) in iPSC-derived neural progenitor cells is sufficient to rapidly generate O4(+) OL with an efficiency of up to 70% in 28 d and a global gene-expression profile comparable to primary human OL...
March 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28241049/expression-of-cd133-and-cd44-in-glioblastoma-stem-cells-correlates-with-cell-proliferation-phenotype-stability-and-intra-tumor-heterogeneity
#10
Daniel V Brown, Gulay Filiz, Paul M Daniel, Frédéric Hollande, Sebastian Dworkin, Stephanie Amiridis, Nicole Kountouri, Wayne Ng, Andrew P Morokoff, Theo Mantamadiotis
Glioblastoma (GBM) is a heterogeneous tumor of the brain with a poor prognosis due to recurrence and drug resistance following therapy. Genome-wide profiling has revealed the existence of distinct GBM molecular subtypes that respond differently to aggressive therapies. Despite this, molecular subtype does not predict recurrence or drug resistance and overall survival is similar across subtypes. One of the key features contributing to tumor recurrence and resistance to therapy is proposed to be an underlying subpopulation of resistant glioma stem cells (GSC)...
2017: PloS One
https://www.readbyqxmd.com/read/28230075/oxygen-impairs-oligodendroglial-development-via-oxidative-stress-and-reduced-expression-of-hif-1%C3%AE
#11
Christina Brill, Till Scheuer, Christoph Bührer, Stefanie Endesfelder, Thomas Schmitz
The premature increase of oxygen tension may contribute to oligodendroglial precursor cell (OPC) damage in preterm infants. Fetal OPCs are exposed to low oxygen tissue tensions not matched when cells are cultured in room air. Maturation (A2B5, O4, O1, MBP, CNP, arborization), oxidative stress (nitrotyrosine Western blot, NRF2 and SOD2 expression), apoptosis (TUNEL), proliferation (Ki67), and expression of transcription factors regulated by Hypoxia-Inducible-Factor-1-alpha (Hif-1α) expressed in OPCs (Olig1, Olig2, Sox9, Sox10) were assessed in rat OPCs and OLN93 cells cultured at 5% O2 and 21% O2...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28161197/icariin-enhances-remyelination-process-after-acute-demyelination-induced-by-cuprizone-exposure
#12
Yifan Zhang, Linlin Yin, Na Zheng, Li Zhang, Jianghong Liu, Weixiong Liang, Qi Wang
Pathology are still progressive and cumulative in the remission course of relapsing-remitting MS (RRMS), thus drug treatment during the remission period may play a great role for the regeneration of the myelin sheath. C57BL/6 mice were fed with cuprizone (CPZ, 0.2% w/w) for 5 weeks to induce acute demyelination and oligodendrocytes degeneration, after which CPZ was withdrawn to allow recovery. Icariin (ICA, 6.25, 12.5 and 25mg/kg/day), vehicle (0.5% sodium carboxymethyl cellulose solution) or water was administrated orally to mice for 1 week after CPZ withdrawal...
February 1, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28148827/mutant-idh1-disrupts-the-mouse-subventricular-zone-and-alters-brain-tumor-progression
#13
Christopher J Pirozzi, Austin B Carpenter, Matthew S Waitkus, Catherine Y Wang, Huishan Zhu, Landon J Hansen, Lee H Chen, Paula K Greer, Jie Feng, Yu Wang, Cheryl B Bock, Ping Fan, Ivan Spasojevic, Roger E McLendon, Darell D Bigner, Yiping He, Hai Yan
IDH1 mutations occur in the majority of low-grade gliomas and lead to the production of the oncometabolite, D-2-hydroxyglutarate (D-2HG). To understand the effects of tumor-associated mutant IDH1 (IDH1-R132H) on both the neural stem cell (NSC) population and brain tumorigenesis, genetically faithful cell lines and mouse model systems were generated. Here, it is reported that mouse NSCs expressing Idh1-R132H displayed reduced proliferation due to p53-mediated cell cycle arrest as well as a decreased ability to undergo neuronal differentiation...
February 1, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28122245/oncogenes-activate-an-autonomous-transcriptional-regulatory-circuit-that-drives-glioblastoma
#14
Dinesh K Singh, Rahul K Kollipara, Vamsidara Vemireddy, Xiao-Li Yang, Yuxiao Sun, Nanda Regmi, Stefan Klingler, Kimmo J Hatanpaa, Jack Raisanen, Steve K Cho, Shyam Sirasanagandla, Suraj Nannepaga, Sara Piccirillo, Tomoyuki Mashimo, Shan Wang, Caroline G Humphries, Bruce Mickey, Elizabeth A Maher, Hongwu Zheng, Ryung S Kim, Ralf Kittler, Robert M Bachoo
Efforts to identify and target glioblastoma (GBM) drivers have primarily focused on receptor tyrosine kinases (RTKs). Clinical benefits, however, have been elusive. Here, we identify an SRY-related box 2 (SOX2) transcriptional regulatory network that is independent of upstream RTKs and capable of driving glioma-initiating cells. We identified oligodendrocyte lineage transcription factor 2 (OLIG2) and zinc-finger E-box binding homeobox 1 (ZEB1), which are frequently co-expressed irrespective of driver mutations, as potential SOX2 targets...
January 24, 2017: Cell Reports
https://www.readbyqxmd.com/read/28070830/mesenchymal-subtype-of-glioblastomas-with-high-dna-pkcs-expression-is-associated-with-better-response-to-radiotherapy-and-temozolomide
#15
Baptiste Pinel, Mathilde Duchesne, Julie Godet, Serge Milin, Antoine Berger, Michel Wager, Lucie Karayan-Tapon
A better understanding of the relationship between glioblastomas molecular subtypes and radio-chemotherapy is needed for the development of individualized strategies. In this study, we aimed to assess whether non-homologous end-joining (NHEJ) protein expression is associated and could predict responses to treatment of mesenchymal (MES) and proneural (PN) subtypes. Tumors from 122 patients with a glioblastoma treated at the University Hospital of Poitiers between 2002-2013 by an association of radiotherapy and temozolomide were collected...
January 10, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28058491/evaluating-the-impact-of-genetic-and-epigenetic-aberrations-on-survival-and-response-in-acute-myeloid-leukemia-patients-receiving-epigenetic-therapy
#16
RANDOMIZED CONTROLLED TRIAL
Jan K Hiller, Claudia Schmoor, Verena I Gaidzik, Charlotte Schmidt-Salzmann, Arzu Yalcin, Mahmoud Abdelkarim, Nadja Blagitko-Dorfs, Konstanze Döhner, Lars Bullinger, Justus Duyster, Michael Lübbert, Björn Hackanson
Treatment with hypomethylating agents such as decitabine, which results in overall response rates of up to 50%, has become standard of care in older patients with acute myeloid leukemia (AML) who are not candidates for intensive chemotherapy. However, there still exists a lack of prognostic and predictive molecular biomarkers that enable selection of patients who are likely to benefit from epigenetic therapy. Here, we investigated distinct genetic (FLT3-ITD, NPM1, DNMT3A) and epigenetic (estrogen receptor alpha (ERα), C/EBPα, and OLIG2) aberrations in 87 AML patients from the recently published phase II decitabine trial (AML00331) to identify potential biomarkers for patients receiving hypomethylating therapy...
April 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28035478/metformin-attenuates-cognitive-impairments-in-hypoxia-ischemia-neonatal-rats-via-improving-remyelination
#17
Boxiang Qi, Libao Hu, Lei Zhu, Lei Shang, Liping Sheng, Xuecheng Wang, Na Liu, Nana Wen, Xiaohe Yu, Qihong Wang, Yujia Yang
Perinatal hypoxia-ischemia (H/I) causes brain injury and myelination damage. Finding efficient methods to restore myelination is critical for the recovery of brain impairments. By applying an H/I rat model, we demonstrate that metformin (Met) treatment significantly ameliorates the loss of locomotor activity and cognition of H/I rat in the Morris water maze and open field task tests. After administration of Met to H/I rat, the proliferation of Olig2+ oligodendrocyte progenitor cells and the expression of myelin basic protein are obviously increased in the corpus callosum...
December 29, 2016: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28001323/prenatal-transplantation-of-epidermal-neural-crest-stem-cells-in-malformation-of-cortical-development-mouse-model
#18
Ameneh Omidi, Mohammad Akbari, Keywan Mortezaee, Ehsan Eqlimi, Cordian Beyer, Adib Zendedel, Iraj Ragerdi Kashani
Prenatal interventions may offer an immense opportunity in therapeutic protocols of malformations of cortical development (MCD). Epidermal neural crest stem cells (EPI-NCSCs) of the hair follicle bulge exhibit features of both embryonic and adult stem cells; these cells maintain their neurologic differentiation capability because of their neural crest origin. However, it is unknown if prenatal use of EPI-NCSCs could be beneficial in targeting methylazoxymethanol (MAM)-induced MCD, which further addressed in the present work...
December 21, 2016: Microscopy Research and Technique
https://www.readbyqxmd.com/read/27923998/interplay-between-h1-and-hmgn-epigenetically-regulates-olig1-2-expression-and-oligodendrocyte-differentiation
#19
Tao Deng, Yuri Postnikov, Shaofei Zhang, Lillian Garrett, Lore Becker, Ildikó Rácz, Sabine M Hölter, Wolfgang Wurst, Helmut Fuchs, Valerie Gailus-Durner, Martin Hrabe de Angelis, Michael Bustin
An interplay between the nucleosome binding proteins H1 and HMGN is known to affect chromatin dynamics, but the biological significance of this interplay is still not clear. We find that during embryonic stem cell differentiation loss of HMGNs leads to down regulation of genes involved in neural differentiation, and that the transcription factor OLIG2 is a central node in the affected pathway. Loss of HMGNs affects the expression of OLIG2 as well as that of OLIG1, two transcription factors that are crucial for oligodendrocyte lineage specification and nerve myelination...
December 6, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27911079/trans-acting-epigenetic-effects-of-chromosomal-aneuploidies-lessons-from-down-syndrome-and-mouse-models
#20
Catherine Do, Zhuo Xing, Y Eugene Yu, Benjamin Tycko
An important line of postgenomic research seeks to understand how genetic factors can influence epigenetic patterning. Here we review epigenetic effects of chromosomal aneuploidies, focusing on findings in Down syndrome (DS, trisomy 21). Recent work in human DS and mouse models has shown that the extra chromosome 21 acts in trans to produce epigenetic changes, including differential CpG methylation (DS-DM), in specific sets of downstream target genes, mostly on other chromosomes. Mechanistic hypotheses emerging from these data include roles of chromosome 21-linked methylation pathway genes (DNMT3L and others) and transcription factor genes (RUNX1, OLIG2, GABPA, ERG and ETS2) in shaping the patterns of DS-DM...
February 2017: Epigenomics
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