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https://www.readbyqxmd.com/read/29449625/toll-like-receptor-4-modulation-influences-human-neural-stem-cell-proliferation-and-differentiation
#1
Chiara Grasselli, Daniela Ferrari, Cristina Zalfa, Matias Soncini, Gianluigi Mazzoccoli, Fabio A Facchini, Laura Marongiu, Francesca Granucci, Massimiliano Copetti, Angelo Luigi Vescovi, Francesco Peri, Lidia De Filippis
Toll-like receptor 4 (TLR4) activation is pivotal to innate immunity and has been shown to regulate proliferation and differentiation of human neural stem cells (hNSCs) in vivo. Here we study the role of TLR4 in regulating hNSC derived from the human telencephalic-diencephalic area of the fetal brain and cultured in vitro as neurospheres in compliance with Good Manifacture Procedures (GMP) guidelines. Similar batches have been used in recent clinical trials in ALS patients. We found that TLR2 and 4 are expressed in hNSCs as well as CD14 and MD-2 co-receptors, and TLR4 expression is downregulated upon differentiation...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29445239/the-urokinase-receptor-induces-a-mesenchymal-gene-expression-signature-in-glioblastoma-cells-and-promotes-tumor-cell-survival-in-neurospheres
#2
Andrew S Gilder, Letizia Natali, Danielle M Van Dyk, Cristina Zalfa, Michael A Banki, Donald P Pizzo, Huawei Wang, Richard L Klemke, Elisabetta Mantuano, Steven L Gonias
PLAUR encodes the urokinase receptor (uPAR), which promotes cell survival, migration, and resistance to targeted cancer therapeutics in glioblastoma cells in culture and in mouse model systems. Herein, we show that patient survival correlates inversely with PLAUR mRNA expression in gliomas of all grades, in glioblastomas, and in the subset of glioblastomas that demonstrate the mesenchymal gene expression signature. PLAUR clusters with genes that define the more aggressive mesenchymal subtype in transcriptome profiles of glioblastoma tissue and glioblastoma cells in neurospheres, which are enriched for multipotent cells with stem cell-like qualities...
February 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29443896/dexamethasone-mediated-upregulation-of-calreticulin-inhibits-primary-human-glioblastoma-dispersal-ex-vivo
#3
Mohan Nair, Juan Romero, Aria Mahtabfar, Ahmed M Meleis, Ramsey A Foty, Siobhan A Corbett
Dispersal of Glioblastoma (GBM) renders localized therapy ineffective and is a major cause of recurrence. Previous studies have demonstrated that Dexamethasone (Dex), a drug currently used to treat brain tumor-related edema, can also significantly reduce dispersal of human primary GBM cells from neurospheres. It does so by triggering α5 integrin activity, leading to restoration of fibronectin matrix assembly (FNMA), increased neurosphere cohesion, and reduction of neurosphere dispersal velocity (DV). How Dex specifically activates α5 integrin in these GBM lines is unknown...
February 14, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29443090/native-chromatin-immunoprecipitation-using-murine-brain-tumor-neurospheres
#4
Flor M Mendez, Felipe J Núñez, Rocío I Zorrilla-Veloz, Pedro R Lowenstein, Maria G Castro
Epigenetic modifications may be involved in the development and progression of glioma. Changes in methylation and acetylation of promoters and regulatory regions of oncogenes and tumor suppressors can lead to changes in gene expression and play an important role in the pathogenesis of brain tumors. Native chromatin immunoprecipitation (ChIP) is a popular technique that allows the detection of modifications or other proteins tightly bound to DNA. In contrast to cross-linked ChIP, in native ChIP, cells are not treated with formaldehyde to covalently link protein to DNA...
January 29, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29438802/endocannabinoid-signaling-in-embryonic-neuronal-motility-and-cell-cell-contact-role-of-mglur5-and-trpc3-channels
#5
Pauli M Turunen, Lauri M Louhivuori, Verna Louhivuori, Jyrki P Kukkonen, Karl E Åkerman
Cell-cell communication plays a central role in the guidance of migrating neuronal precursor cells during the development of the cerebral cortex. Endocannabinoids (eCBs) have previously been shown to be one of the central factors regulating neuronal migration. In this study the effects of eCBs on different parameters, expected to affect embryonic cortical neuronal motility have been analyzed in neurosphere derived neuroblasts using time-lapse microscopy. Increased endogenous production of the endocannabinoid 2-arachidonyl glycerol (2-AG) causes bursts of neuroblast motility...
February 10, 2018: Neuroscience
https://www.readbyqxmd.com/read/29436662/comparison-of-the-properties-of-neural-stem-cells-of-the-hippocampus-in-the-tree-shrew-and-rat-in%C3%A2-vitro
#6
Yuan-Dong Hu, Qiong Zhao, Xue-Rong Zhang, Liu-Lin Xiong, Zi-Bin Zhang, Piao Zhang, Rong-Ping Zhang, Ting-Hua Wang
Neural stem cells (NSCs) are characterized by the ability of self‑renewal and capacity to proliferate and produce new nervous tissue. NSCs are capable of differentiating to three lineages of neural cells, including neurons, oligodendrocytes and astrocytes. Furthermore, hippocampal NSCs transplantation can improve the neurological deficits associated with expression of cytokines. Therefore, to compare the properties of NSCs of tree shrews and rats in vitro, NSCs from tree shrews (tsNSCs) and rats f(rNSCs) were isolated...
February 12, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29415247/polycomb-protein-eed-is-required-for-neurogenesis-and-cortical-injury-activation-in-the-subventricular-zone
#7
Bin Sun, Eunhyuk Chang, Anna Gerhartl, Francis G Szele
The postnatal subventricular zone (SVZ) harbors neural stem cells (NSCs) that exhibit robust neurogenesis. However, the epigenetic mechanisms that maintain NSCs and regulate neurogenesis remain unclear. We report that label-retaining SVZ NSCs express Eed, the core component of Polycomb repressive complex 2. In vivo and in vitro conditional knockout and knockdown show Eed is necessary for maintaining NSC proliferation, neurogenesis and neurosphere formation. We discovered that Eed functions to maintain p21 protein levels in NSCs by repressing Gata6 transcription...
February 3, 2018: Cerebral Cortex
https://www.readbyqxmd.com/read/29396807/the-cns-penetrating-taxane-tpi-287-and-the-aurka-inhibitor-alisertib-induce-synergistic-apoptosis-in-glioblastoma-cells
#8
Cory T Zumbar, Aisulu Usubalieva, Paul D King, Xiaohui Li, Caroline S Mifsud, Hailey M Dalton, Muge Sak, Sara Urio, William M Bryant, Joseph P McElroy, George Farmer, Norman L Lehman
Glioblastoma is a highly malignant disease in critical need of expanded treatment options. The AURKA inhibitor alisertib exhibits antiproliferative activity against glioblastoma in vitro and in vivo. Unlike current clinically used taxane drugs, the novel taxane TPI 287 penetrates the CNS. We tested for interactions between three selective AURKA inhibitors and TPI 287 against standard U87 and U1242 cells and primary glioblastoma neurospheres using colony formation assays. Bliss and Chou-Talalay analyses were utilized to statistically test for synergism...
February 2, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29359518/store-operated-calcium-entries-control-neural-stem-cell-self-renewal-in-the-adult-brain-subventricular-zone
#9
Florence Domenichini, Elodie Terrié, Patricia Arnault, Thomas Harnois, Christophe Magaud, Patrick Bois, Bruno Constantin, Valérie Coronas
The subventricular zone (SVZ) is the major stem cell niche in the brain of adult mammals. Within this region, neural stem cells proliferate, self-renew and give birth to neurons and glial cells. Previous studies underlined enrichment in calcium signaling-related transcripts in adult neural stem cells. Because of their ability to mobilize sustained calcium influxes in response to a wide range of extracellular factors, store-operated channels (SOC) appear to be, among calcium channels, relevant candidates to induce calcium signaling in neural stem cells whose cellular activities are continuously adapted to physiological signals from the microenvironment...
January 23, 2018: Stem Cells
https://www.readbyqxmd.com/read/29352135/blocking-zika-virus-vertical-transmission
#10
Pinar Mesci, Angela Macia, Spencer M Moore, Sergey A Shiryaev, Antonella Pinto, Chun-Teng Huang, Leon Tejwani, Isabella R Fernandes, Nicole A Suarez, Matthew J Kolar, Sandro Montefusco, Scott C Rosenberg, Roberto H Herai, Fernanda R Cugola, Fabiele B Russo, Nicholas Sheets, Alan Saghatelian, Sujan Shresta, Jeremiah D Momper, Jair L Siqueira-Neto, Kevin D Corbett, Patricia C B Beltrão-Braga, Alexey V Terskikh, Alysson R Muotri
The outbreak of the Zika virus (ZIKV) has been associated with increased incidence of congenital malformations. Although recent efforts have focused on vaccine development, treatments for infected individuals are needed urgently. Sofosbuvir (SOF), an FDA-approved nucleotide analog inhibitor of the Hepatitis C (HCV) RNA-dependent RNA polymerase (RdRp) was recently shown to be protective against ZIKV both in vitro and in vivo. Here, we show that SOF protected human neural progenitor cells (NPC) and 3D neurospheres from ZIKV infection-mediated cell death and importantly restored the antiviral immune response in NPCs...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29345353/hipop-mesenchymal-population-has-high-potential-for-repairing-injured-peripheral-nerves
#11
Yukako Yamauchi, Shousaku Itoh, Haruna Naruse, Yuki Itoh, Makoto Abe, Takumi Kagioka, Mikako Hayashi
Bone marrow stromal cells (BMSCs) are reportedly a heterogeneous population of mesenchymal stem cells (MSCs). Recently, we developed a simple strategy for the enrichment of MSCs with the capacity to differentiate into osteoblasts, chondrocytes, and adipocytes. On transplantation, the progenitor-enriched fractions can regenerate the bone with multiple lineages of donor origin and are thus called "highly purified osteoprogenitors" (HipOPs). Although our previous studies have demonstrated that HipOPs are enriched with MSCs and exhibit a higher potential to differentiate into osteoblasts, adipocytes, and chondrocytes than BMSCs, their potential to differentiate into neural cells has not been clarified...
January 18, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29321665/fhl2-interacts-with-egfr-to-promote-glioblastoma-growth
#12
Lili Sun, Shuye Yu, Hui Xu, Yanwen Zheng, Juntang Lin, Meiyan Wu, Jide Wang, Aidong Wang, Qing Lan, Frank Furnari, Webster Cavenee, Benjamin Purow, Ming Li
Four-and-a-half LIM protein2 (FHL2) is a member of the LIM-only protein family, which plays a critical role in tumorigenesis. We previously reported that FHL2 is upregulated and plays an oncogenic role in glioblastoma (GBM), the most common and aggressive brain tumor. GBM is also marked by amplification of the epidermal growth factor receptor (EGFR) gene and its mutations, of which EGFRvIII is the most common and functionally significant. Here we report that FHL2 physically interacts with the wild-type EGFR and its mutated EGFRvIII form in GBM cells...
January 11, 2018: Oncogene
https://www.readbyqxmd.com/read/29312819/small-scale-screening-of-anticancer-drugs-acting-specifically-on-neural-stem-progenitor-cells-derived-from-human-induced-pluripotent-stem-cells-using-a-time-course-cytotoxicity-test
#13
Hayato Fukusumi, Yukako Handa, Tomoko Shofuda, Yonehiro Kanemura
Since the development of human-induced pluripotent stem cells (hiPSCs), various types of hiPSC-derived cells have been established for regenerative medicine and drug development. Neural stem/progenitor cells (NSPCs) derived from hiPSCs (hiPSC-NSPCs) have shown benefits for regenerative therapy of the central nervous system. However, owing to their intrinsic proliferative potential, therapies using transplanted hiPSC-NSPCs carry an inherent risk of undesired growth in vivo. Therefore, it is important to find cytotoxic drugs that can specifically target overproliferative transplanted hiPSC-NSPCs without damaging the intrinsic in vivo stem-cell system...
2018: PeerJ
https://www.readbyqxmd.com/read/29312541/energy-metabolism-in-glioblastoma-stem-cells-ppar%C3%AE-a-metabolic-adaptor-to-intratumoral-microenvironment
#14
Alessia Fidoamore, Loredana Cristiano, Chiara Laezza, Renato Galzio, Elisabetta Benedetti, Benedetta Cinque, Andrea Antonosante, Michele d'Angelo, Vanessa Castelli, Maria Grazia Cifone, Rodolfo Ippoliti, Antonio Giordano, Annamaria Cimini
Glioblastoma (GB), the most-common cancer in the adult brain, despite surgery and radio/ chemotherapy, is to date almost incurable. Many hypoxic tumors, including GB, show metabolic reprogramming to sustain uncontrolled proliferation, hypoxic conditions and angiogenesis. Peroxisome Proliferator-activated Receptors (PPAR), particularly the α isotype, have been involved in the control of energetic metabolism. Herein, we characterized patient-derived GB neurospheres focusing on their energetic metabolism and PPARα expression...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29288440/functional-requirement-of-a-wild-type-allele-for-mutant-idh1-to-suppress-anchorage-independent-growth-through-redox-homeostasis
#15
Patricia D B Tiburcio, Bing Xiao, Shauna Berg, Sydney Asper, Sean Lyne, Yan Zhang, Xingen Zhu, Hai Yan, L Eric Huang
Mutations of isocitrate dehydrogenase 1 (IDH1) gene are most common in glioma, arguably preceding all known genetic alterations during tumor development. IDH1 mutations nearly invariably target the enzymatic active site Arg132, giving rise to the predominant IDH1R132H. Cells harboring IDH1 R132H -heterozygous mutation produce 2-hydroxyglutarate (2-HG), which results in histone and DNA hypermethylation. Although exogenous IDH1 R132H transduction has been shown to promote anchorage-independent growth, the biological role of IDH1R132H in glioma remains debatable...
December 29, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/29287093/direct-exposure-to-mild-heat-promotes-proliferation-and-neuronal-differentiation-of-neural-stem-progenitor-cells-in-vitro
#16
Md Emon Hossain, Kentaro Matsuzaki, Masanori Katakura, Naotoshi Sugimoto, Abdullah Al Mamun, Rafiad Islam, Michio Hashimoto, Osamu Shido
Heat acclimation in rats is associated with enhanced neurogenesis in thermoregulatory centers of the hypothalamus. To elucidate the mechanisms for heat acclimation, we investigated the effects of direct mild heat exposure on the proliferation and differentiation of neural stem/progenitor cells (NSCs/NPCs). The NSCs/NPCs isolated from forebrain cortices of 14.5-day-old rat fetuses were propagated as neurospheres at either 37.0°C (control) or 38.5°C (mild heat exposure) for four days, and the effects on proliferation were investigated by MTS cell viability assay, measurement of neurosphere diameter, and counting the total number of cells...
2017: PloS One
https://www.readbyqxmd.com/read/29279741/generation-of-induced-pluripotent-stem-cells-and-neural-stem-progenitor-cells-from-newborns-with-spina-bifida-aperta
#17
Yohei Bamba, Masahiro Nonaka, Natsu Sasaki, Tomoko Shofuda, Daisuke Kanematsu, Hiroshi Suemizu, Yuichiro Higuchi, Ritsuko K Pooh, Yonehiro Kanemura, Hideyuki Okano, Mami Yamasaki
Study Design: We established induced pluripotent stem cells (iPSCs) and neural stem/progenitor cells (NSPCs) from three newborns with spina bifida aperta (SBa) using clinically practical methods. Purpose: We aimed to develop stem cell lines derived from newborns with SBa for future therapeutic use. Overview of Literature: SBa is a common congenital spinal cord abnormality that causes defects in neurological and urological functions. Stem cell transplantation therapies are predicted to provide beneficial effects for patients with SBa...
December 2017: Asian Spine Journal
https://www.readbyqxmd.com/read/29258522/nfat1-regulated-il6-signalling-contributes-to-aggressive-phenotypes-of-glioma
#18
Yang Jiang, Sheng Han, Wen Cheng, Zixun Wang, Anhua Wu
BACKGROUND: We previously demonstrated that the local immune status correlated with the glioma prognosis. Interleukin-6 (IL6) was identified as an important local immune-related risk marker related to unfavourable prognosis. In this study, we further investigated the role and regulation of IL6 signalling in glioma. METHODS: The expression and prognostic value of IL6 and the IL6 receptor (IL6R) were explored in The Cancer Genome Atlas (TCGA) and REMBRANDT databases and clinical samples...
December 19, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29258295/therapeutic-targeting-of-ependymoma-as-informed-by-oncogenic-enhancer-profiling
#19
Stephen C Mack, Kristian W Pajtler, Lukas Chavez, Konstantin Okonechnikov, Kelsey C Bertrand, Xiuxing Wang, Serap Erkek, Alexander Federation, Anne Song, Christine Lee, Xin Wang, Laura McDonald, James J Morrow, Alina Saiakhova, Patrick Sin-Chan, Qiulian Wu, Kulandaimanuvel Antony Michaelraj, Tyler E Miller, Christopher G Hubert, Marina Ryzhova, Livia Garzia, Laura Donovan, Stephen Dombrowski, Daniel C Factor, Betty Luu, Claudia L L Valentim, Ryan C Gimple, Andrew Morton, Leo Kim, Briana C Prager, John J Y Lee, Xiaochong Wu, Jennifer Zuccaro, Yuan Thompson, Borja L Holgado, Jüri Reimand, Susan Q Ke, Adam Tropper, Sisi Lai, Senthuran Vijayarajah, Sylvia Doan, Vaidehi Mahadev, Ana Fernandez Miñan, Susanne N Gröbner, Matthias Lienhard, Marc Zapatka, Zhiqin Huang, Kenneth D Aldape, Angel M Carcaboso, Peter J Houghton, Stephen T Keir, Till Milde, Hendrik Witt, Yan Li, Chao-Jun Li, Xiu-Wu Bian, David T W Jones, Ian Scott, Sheila K Singh, Annie Huang, Peter B Dirks, Eric Bouffet, James E Bradner, Vijay Ramaswamy, Nada Jabado, James T Rutka, Paul A Northcott, Mathieu Lupien, Peter Lichter, Andrey Korshunov, Peter C Scacheri, Stefan M Pfister, Marcel Kool, Michael D Taylor, Jeremy N Rich
Genomic sequencing has driven precision-based oncology therapy; however, the genetic drivers of many malignancies remain unknown or non-targetable, so alternative approaches to the identification of therapeutic leads are necessary. Ependymomas are chemotherapy-resistant brain tumours, which, despite genomic sequencing, lack effective molecular targets. Intracranial ependymomas are segregated on the basis of anatomical location (supratentorial region or posterior fossa) and further divided into distinct molecular subgroups that reflect differences in the age of onset, gender predominance and response to therapy...
December 20, 2017: Nature
https://www.readbyqxmd.com/read/29249301/ng2-and-gfap-co-expression-after-differentiation-in-cells-transfected-with-mutant-gfap-and-in-undifferentiated-glioma-cells
#20
U Gómez-Pinedo, S Sirerol-Piquer, M Durán-Moreno, J A Matias-Guiu, J A Barcia, J M García-Verdugo, J Matias-Guiu
INTRODUCTION: Alexander disease is a rare disorder caused by mutations in the gene coding for glial fibrillary acidic protein (GFAP). In a previous study, differentiation of neurospheres transfected with these mutations resulted in a cell type that expresses both GFAP and NG2. OBJECTIVE: To determine the effect of molecular marker mutations in comparison to undifferentiated glioma cells simultaneously expressing GFAP and NG2. METHODS: We used samples of human glioblastoma (GBM) and rat neurospheres transfected with GFAP mutations to analyse GFAP and NG2 expression after differentiation...
December 14, 2017: Neurología: Publicación Oficial de la Sociedad Española de Neurología
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