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  • 1
    Language: English
    In: Nature neuroscience, August 2018, Vol.21(8), pp.1139
    Description: In the version of this article initially published online, there were errors in URLs for www.southernbiotech.com, appearing in Methods sections "m6A dot-blot" and "Western blot analysis." The first two URLs should be https://www.southernbiotech.com/?catno=4030-05&type=Polyclonal#&panel1-1 and the third should be https://www.southernbiotech.com/?catno=6170-05&type=Polyclonal. In addition, some Methods URLs for bioz.com, www.abcam.com and www.sysy.com were printed correctly but not properly linked. The errors have been corrected in the PDF and HTML versions of this article.
    Keywords: Neural Stem Cells ; RNA Modification ; Ribonucleic Acid–RNA ; Stem Cells;
    ISSN: 10976256
    E-ISSN: 1546-1726
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  • 2
    Language: English
    In: Science (New York, N.Y.), 19 December 2014, Vol.346(6216), pp.1458-9
    Description: Diffuse intrinsic pontine glioma (DIPG) is an incurable pediatric brain tumor. About 80% of these tumors contain mutations in genes that encode histones (H3.3 or H3.1) ( 1 , 2 ), proteins that package DNA into chromatin. These mutations, which change lysine 27 to methionine (K27M), are believed to sequester Polycomb repressive complex 2 (PRC2), which normally represses gene expression through histone methylation (see the figure). In the absence of PRC2, genes that should be silent are expressed, which is thought to drive cell transformation ( 3 – 5 ). However, the precise role of histone mutations in tumorigenesis is unclear, and strategies to target the mutations remain elusive. As reported by Funato et al. on page 1529 of this issue ( 6 ), as well as by Hashizume et al. ( 7 ), models of K27M-mutant DIPG can be used to elucidate the mechanisms of transformation and to identify new approaches to therapy.
    Keywords: Models, Genetic ; Brain Stem Neoplasms -- Genetics ; Cell Transformation, Neoplastic -- Genetics ; Embryonic Stem Cells -- Metabolism ; Glioma -- Genetics ; Histones -- Genetics ; Neural Stem Cells -- Metabolism
    ISSN: 00368075
    E-ISSN: 1095-9203
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  • 3
    Language: English
    In: Cancer Research, 12/01/2015, Vol.75(23 Supplement), pp.A46-A46
    ISSN: 0008-5472
    E-ISSN: 1538-7445
    Source: CrossRef
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  • 4
    Language: English
    In: Cancer Research, 10/01/2014, Vol.74(19 Supplement), pp.LB-203-LB-203
    ISSN: 0008-5472
    E-ISSN: 1538-7445
    Source: CrossRef
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  • 5
    Language: English
    In: Nature neuroscience, February 2018, Vol.21(2), pp.195-206
    Description: Internal N-methyladenosine (mA) modification is widespread in messenger RNAs (mRNAs) and is catalyzed by heterodimers of methyltransferase-like protein 3 (Mettl3) and Mettl14. To understand the role of mA in development, we deleted Mettl14 in embryonic neural stem cells (NSCs) in a mouse model. Phenotypically, NSCs lacking Mettl14 displayed markedly decreased proliferation and premature differentiation, suggesting that mA modification enhances NSC self-renewal. Decreases in the NSC pool led to a decreased number of late-born neurons during cortical neurogenesis. Mechanistically, we discovered a genome-wide increase in specific histone modifications in Mettl14 knockout versus control NSCs. These changes correlated with altered gene expression and observed cellular phenotypes, suggesting functional significance of altered histone modifications in knockout cells. Finally, we found that mA regulates histone modification in part by destabilizing transcripts that encode histone-modifying enzymes. Our results suggest an essential role for mA in development and reveal mA-regulated histone modifications as a previously unknown mechanism of gene regulation in mammalian cells.
    Keywords: Cell Self Renewal -- Genetics ; Deoxyadenosines -- Genetics ; Gene Expression Regulation, Developmental -- Physiology ; Histones -- Metabolism ; Neural Stem Cells -- Physiology ; RNA, Messenger -- Metabolism
    ISSN: 10976256
    E-ISSN: 1546-1726
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  • 6
    Language: English
    In: Trends in Neurosciences, 2001, Vol.24(12), pp.680-682
    Description: Cerebellar granule cells are the most abundant neurons in the brain and are crucial to the circuitry that controls motor coordination. The proliferation of granule cell precursors (GCPs) is controlled by the secreted signaling molecule Sonic hedgehog (Shh), but the factors that regulate GCP differentiation remain a mystery. A recent study suggests that the extracellular matrix protein vitronectin might tell GCPs when to stop dividing and begin differentiation. The extracellular matrix protein vitronectin might be involved in the signal that tells granule cell precursors to stop dividing and when to start differentiation.
    Keywords: Neuroscience ; Development ; Medicine ; Anatomy & Physiology
    ISSN: 0166-2236
    E-ISSN: 1878-108X
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  • 7
    Language: English
    In: Cancer Cell, 17 January 2012, Vol.21(1), pp.1-3
    Description: The capacity for self-renewal is thought to be a critical property of tumor-initiating cells. This capacity is often associated with the ability to generate spheres in vitro. In this issue of , Barrett et al. show that cells lacking sphere-forming ability can still be very efficient at propagating tumors.
    Keywords: Medicine
    ISSN: 1535-6108
    E-ISSN: 1878-3686
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  • 8
    Language: English
    In: Journal of medicinal chemistry, 28 April 2016, Vol.59(8), pp.3635-49
    Description: Itraconazole (ITZ) is an FDA-approved member of the triazole class of antifungal agents. Two recent drug repurposing screens identified ITZ as a promising anticancer chemotherapeutic that inhibits both the angiogenesis and hedgehog (Hh) signaling pathways. We have synthesized and evaluated first- and second-generation ITZ analogues for their anti-Hh and antiangiogenic activities to probe more fully the structural requirements for these anticancer properties. Our overall results suggest that the triazole functionality is required for ITZ-mediated inhibition of angiogenesis but that it is not essential for inhibition of Hh signaling. The synthesis and evaluation of stereochemically defined des-triazole ITZ analogues also provides key information as to the optimal configuration around the dioxolane ring of the ITZ scaffold. Finally, the results from our studies suggest that two distinct cellular mechanisms of action govern the anticancer properties of the ITZ scaffold.
    Keywords: Antifungal Agents -- Therapeutic Use ; Antineoplastic Agents -- Therapeutic Use ; Itraconazole -- Therapeutic Use
    ISSN: 00222623
    E-ISSN: 1520-4804
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  • 9
    Language: English
    In: Nature Neuroscience, 2013, Vol.16(12), p.1737(9)
    Description: It is generally believed that cerebellar granule neurons originate exclusively from granule neuron precursors (GNPs) in the external germinal layer (EGL). Here we identified a rare population of neuronal progenitors in mouse developing cerebellum that expresses Nestin. Although Nestin is widely considered a marker for multipotent stem cells, these Nestin-expressing progenitors (NEPs) are committed to the granule neuron lineage. Unlike conventional GNPs, which reside in the outer EGL and proliferate extensively, NEPs reside in the deep part of the EGL and are quiescent. Expression profiling revealed that NEPs are distinct from GNPs and, in particular, express markedly reduced levels of genes associated with DNA repair. Consistent with this, upon aberrant activation of Sonic hedgehog (Shh) signaling, NEPs exhibited more severe genomic instability and gave rise to tumors more efficiently than GNPs. These studies revealed a previously unidentified progenitor for cerebellar granule neurons and a cell of origin for medulloblastoma.
    Keywords: Cerebellum – Research ; Cerebellum – Physiological Aspects ; Gene Expression – Research ; Intermediate Filament Proteins – Health Aspects ; Intermediate Filament Proteins – Research ; Oncogenic Viruses – Health Aspects ; Oncogenic Viruses – Research
    ISSN: 1097-6256
    E-ISSN: 15461726
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  • 10
    In: Nature Neuroscience, 2013, Vol.16(12), p.1737
    Description: It is generally believed that cerebellar granule neurons originate exclusively from granule neuron precursors (GNPs) in the external germinal layer (EGL). Here we identified a rare population of neuronal progenitors in mouse developing cerebellum that expresses Nestin. Although Nestin is widely considered a marker for multipotent stem cells, these Nestin-expressing progenitors (NEPs) are committed to the granule neuron lineage. Unlike conventional GNPs, which reside in the outer EGL and proliferate extensively, NEPs reside in the deep part of the EGL and are quiescent. Expression profiling revealed that NEPs are distinct from GNPs and, in particular, express markedly reduced levels of genes associated with DNA repair. Consistent with this, upon aberrant activation of Sonic hedgehog (Shh) signaling, NEPs exhibited more severe genomic instability and gave rise to tumors more efficiently than GNPs. These studies revealed a previously unidentified progenitor for cerebellar granule neurons and a cell of origin for medulloblastoma.
    Keywords: Cell Transformation, Neoplastic -- Metabolism ; Cerebellum -- Cytology ; Gene Expression Regulation, Neoplastic -- Physiology ; Nestin -- Metabolism ; Neurons -- Physiology ; Stem Cells -- Physiology;
    ISSN: 1097-6256
    E-ISSN: 15461726
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