Abstract:
:Cancer stem cells (CSC) are essential for tumorigenesis. The transcription factor Sox2 is overexpressed in brain gliomas, and is essential to maintain CSC. In mouse high-grade glioma pHGG cells in culture, Sox2 deletion causes cell proliferation arrest and inability to reform tumors after transplantation in vivo; in Sox2-deleted cells, 134 genes are derepressed. To identify genes mediating Sox2 deletion effects, we overexpressed into pHGG cells nine among the most derepressed genes, and identified four genes, Ebf1, Hey2, Zfp423, and Cdkn2b, that strongly reduced cell proliferation in vitro and brain tumorigenesis in vivo. CRISPR/Cas9 mutagenesis of each gene, individually or in combination (Ebf1 + Cdkn2b), significantly antagonized the proliferation arrest caused by Sox2 deletion. The same genes also repressed clonogenicity in primary human glioblastoma-derived CSC-like lines. These experiments identify a network of critical tumor suppressive Sox2-targets whose inhibition by Sox2 is involved in glioma CSC maintenance, defining new potential therapeutic targets.
journal_name
Gliajournal_title
Gliaauthors
Barone C,Buccarelli M,Alessandrini F,Pagin M,Rigoldi L,Sambruni I,Favaro R,Ottolenghi S,Pallini R,Ricci-Vitiani L,Malatesta P,Nicolis SKdoi
10.1002/glia.23914subject
Has Abstractpub_date
2021-03-01 00:00:00pages
579-593issue
3eissn
0894-1491issn
1098-1136journal_volume
69pub_type
杂志文章相关文献
GLIA文献大全abstract::Oligodendroglial cells undergo rapid transcriptional and dynamic morphological transformation in order to effectively myelinate neuronal axons. Olig1, a basic helix-loop-helix transcription factor, functions to promote the transcription of myelin-specific genes and promotes differentiation and (re)myelination. While t...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.22364
更新日期:2012-09-01 00:00:00
abstract::Remyelination is in the center of new therapies for the treatment of multiple sclerosis to resolve and improve disease symptoms and protect axons from further damage. Although remyelination is considered beneficial in the long term, it is not known, whether this is also the case early in lesion formation. Additionally...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.23167
更新日期:2017-08-01 00:00:00
abstract::A growth cone-enriched fraction was prepared from 3-4 day rat cerebra. Examination of the growth cone fraction by electron microscopy revealed numerous structures circular in appearance that contain a number of features common to neuronal growth cones in vivo. The isolated growth cones stimulated a dose-dependent inco...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.440050204
更新日期:1992-01-01 00:00:00
abstract::Microglial cells are the resident macrophages that are involved in brain injuries and infections. Recent studies using transcranial two-photon microscopy have shown that ATP and P2Y receptors mediated rapid chemotactic responses of miroglia to local injury. However, the molecular mechanism for microglial chemotaxis to...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.20500
更新日期:2007-06-01 00:00:00
abstract::Reorganization of the adult dentate gyrus following unilateral entorhinal cortex lesion (ECL) is a well-established model for studying mechanisms of trauma-induced neuronal plasticity. The lesion induces deafferentiation of the outer molecular layer, which is accompanied by a strong astroglial reaction. This glial res...
journal_title:Glia
pub_type: 杂志文章
doi:
更新日期:1999-11-01 00:00:00
abstract::Mouse sciatic nerves from the degeneration-resistant strain C57BL/6/Wld (Ola) were surgically injected with lysolecithin to induce focal demyelination. Three days later they were transected adjacent to the spinal cord to eliminate contact of the axons with their cell bodies. The Na+ channel distribution was assessed b...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.440150211
更新日期:1995-10-01 00:00:00
abstract::Forkhead transcription factor 3 (Foxp3) is critical for generating CD4(+)CD25(+) regulatory T cells. However, its role in microglia has not been identified. Here, we show that Foxp3 is expressed in microglia and is upregulated upon activation. In Foxp3 mutant mice (Foxp3(sf)), microglia release higher levels of inflam...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.21006
更新日期:2010-08-01 00:00:00
abstract::Cannabinoid agonists might serve as neuroprotective agents in neurodegenerative disorders. Here, we examined this hypothesis in a rat model of Huntington's disease (HD) generated by intrastriatal injection of the mitochondrial complex II inhibitor malonate. Our results showed that only compounds able to activate CB2 r...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.20838
更新日期:2009-08-15 00:00:00
abstract::Plaque deposition in Alzheimer's disease (AD) is known to decrease proliferation in neurogenic niches in AD mouse models, but the effects on cell proliferation and differentiation in other brain areas have not been studied in detail. We analyzed cell proliferation in the cortex of wild type (WT) and APPswePS1dE9 trans...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.22295
更新日期:2012-04-01 00:00:00
abstract::The purpose of the present study was to elucidate the expression and regulation of the L-cystine transporter, system x(c) (-), in Müller cells. In this study, newly developed conditionally immortalized rat Müller cell lines (TR-MUL) from transgenic rats harboring the temperature-sensitive SV 40 large T-antigen gene we...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.10253
更新日期:2003-09-01 00:00:00
abstract::Persistence of radial glia within the adult central nervous system is a widespread phenomenon among fish. Based on a series of studies in the teleost species Apteronotus leptorhynchus, we propose that one function of this persistence is the involvement of radial glia in adult neurogenesis, i.e., the generation and fur...
journal_title:Glia
pub_type: 杂志文章,评审
doi:10.1002/glia.10236
更新日期:2003-07-01 00:00:00
abstract::Recent studies have suggested that Nkx6.2/Gtx and Nkx2.2 homeodomain transcription factors are involved in the regulation of oligodendrocyte maturation and/or myelination which occur predominantly in postnatal stages. However, their cellular specificity in postnatal central nervous system has not been characterized an...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.20937
更新日期:2010-03-01 00:00:00
abstract::Accumulating evidence indicates that astrocytes are actively involved in the physiological and pathophysiological functions of the brain. Intracellular Ca2+ signaling, especially Ca2+ release from the endoplasmic reticulum (ER), is considered to be crucial for the regulation of astrocytic functions. Mice with genetic ...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.23531
更新日期:2019-01-01 00:00:00
abstract::Astrocytes are the most numerous cell type within the central nervous system (CNS) and perform a variety of tasks, from axon guidance and synaptic support, to the control of the blood brain barrier and blood flow. To perform these roles, there is a great variety of astrocytes. In this review, we summarize the function...
journal_title:Glia
pub_type: 杂志文章,评审
doi:10.1002/glia.20848
更新日期:2009-09-01 00:00:00
abstract::Neurogenesis persists in the adult subventricular zone (SVZ) of the mammalian brain. During aging, the SVZ neurogenic capacity undergoes a progressive decline, which is attributed to a decrease in the population of neural stem cells (NSCs). However, the behavior of the NSCs that remain in the aged brain is not fully u...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.22642
更新日期:2014-05-01 00:00:00
abstract::External application of bradykinin (BK) to mouse neuroblastoma X mouse fibroblast hybrid NL308 cells and mouse neuroblastoma X rat glioma hybrid NG108-15 cells produced a transient outward (hyperpolarizing) current. In NG108-15 cells, BK also induced an inward (depolarizing) current associated with a decrease in input...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.440030102
更新日期:1990-01-01 00:00:00
abstract::IQSEC3, a guanine nucleotide exchange factor for ADP-ribosylation factors (ARF-GEFs) is specifically expressed at GABAergic synapses, and its loss increases seizure susceptibility in mice. However, the contribution of microglia to initiation and/or progression of seizures in IQSEC3-deficient mice has not been investig...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.23876
更新日期:2020-12-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting predominantly motor neurons. Recent studies suggest that the disease progression of ALS is non-cell-autonomous, although the interaction between neurons and glial cells in different disease stages is not entirely clear. Here, we ...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.21167
更新日期:2011-06-01 00:00:00
abstract::We first classified 12 malignant glioma cell lines into three different groups (types 1-3) with respect to major histocompatibility complex (MHC) class II expression and analyzed each group based on the different expression status of the class II transactivator (CIITA) gene. Glioma type 1 (2 of 12) showed constitutive...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.10343
更新日期:2004-03-01 00:00:00
abstract::We demonstrate that there are significantly more p75 neurotrophin receptor- (NTR)-expressing cells in olfactory ensheathing cell (OEC) primary cultures from olfactory nerve rootlets (ONR), but a greater proportion of O4 antigen- and PSA-NCAM-expressing cells in parallel cultures from the nerve fibre layer of the olfac...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.20154
更新日期:2005-04-01 00:00:00
abstract::Protein tyrosine kinase (PTK) activity is abundant in microglia, but the PTKs that participate in their activation have not been identified. For these studies, we used three paradigms to characterize PTK expression during microglial activation: resting and activated microglia were bulk fractionated from the adult brai...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.10101
更新日期:2002-10-01 00:00:00
abstract::Individuals with neurofibromatosis 1 (NF1) develop low-grade astrocytomas at an increased frequency. To gain insight into the function of the Nf1 gene product as a growth regulator for astrocytes, we examined mice heterozygous for a targeted Nf1 mutation. In our previous studies, we demonstrated increased numbers of p...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/1098-1136(20010315)33:4<314::aid-glia1030>
更新日期:2001-03-15 00:00:00
abstract::Oligodendroglia and Schwann cells synthesize myelin-specific proteins and lipids for the assembly of the highly organized myelin membrane of the motor-sensory axons in the central (CNS) and peripheral nervous system (PNS), respectively, allowing rapid saltatory conduction. The isoforms of the main myelin proteins, the...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.10014
更新日期:2002-01-01 00:00:00
abstract::We have used C6 glial cells (2B clone), early and late passage, as well as advanced passages (8-17) of glial cells derived from aged (18-month-old) mouse cerebral hemispheres (MACH), as model systems for studying glial properties. In this study passages 20-24 were considered "early" and passages 73-90 were considered ...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.440060402
更新日期:1992-01-01 00:00:00
abstract::Signaling through fibroblast growth factor receptors (FGFRs) is essential for many cellular processes including proliferation and migration, as well as differentiation events such as myelination. Anosmin-1 is an extracellular matrix (ECM) glycoprotein that interacts with the fibroblast growth factor receptor 1 (FGFR1)...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.22609
更新日期:2014-03-01 00:00:00
abstract::Severe transient focal cerebral ischemia causes brain infarction with a strong glial reaction. We have studied whether postischemic reactive glial cells express epidermal growth factor receptor (EGFR) following middle cerebral artery occlusion in the rat. We have also looked for signs of proliferating activity, as EGF...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/(sici)1098-1136(199806)23:2<120::aid-glia3
更新日期:1998-06-01 00:00:00
abstract::Transcriptional regulation of the glial fibrillary acidic protein gene (GFAP) is of interest because of its astrocyte specificity and its upregulation in response to CNS injuries. We have used a transgenic approach instead of cell transfection to identify promoter elements of the human GFAP gene, since previous observ...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.22536
更新日期:2013-09-01 00:00:00
abstract::Oligodendrocyte differentiation and myelination involve dramatic changes in cell signaling pathways, gene expression patterns, cell shape, and cytoskeletal organization. In a pilot study investigating CNS angiogenesis, oligodendrocytes were intensely labeled by antisera directed against the C-terminal of Tie-2, a 140-...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.20175
更新日期:2005-05-01 00:00:00
abstract::Microglia are the immune cells of the central nervous system (CNS) and play important roles under physiological and pathophysiological conditions. Activation of microglia has been reported for a variety of CNS diseases and is believed to be involved in inflammation-mediated neurodegeneration. Loss of TGFβ1 results in ...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.22435
更新日期:2013-02-01 00:00:00
abstract::Gamma-secretase is an aspartyl protease composed of four proteins: presenilin (PS), nicastrin (Nct), APH1, and PEN2. These proteins assemble into a membrane complex that cleaves a variety of substrates within the transmembrane domain. The gamma-secretase cleavage products play an important role in various biological p...
journal_title:Glia
pub_type: 杂志文章
doi:10.1002/glia.20638
更新日期:2008-04-01 00:00:00