'Mitogen-Induced Defective Mitosis Transforms Neural Progenitor Cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE207162 | GEO | 2023/06/28
REPOSITORIES: GEO
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Project description:'Mitogen-Induced Defective Mitosis Transforms Neural Progenitor Cells
| PRJNA854043 | ENA
Project description:Neural precursor cells (NPCs) in the mammalian neocortex generate various neuronal and glial cell types in a developmental stage-dependent manner. Most neocortical NPCs lose their neurogenic potential after birth. We have previously shown that high mobility group A (HMGA) proteins confer the neurogenic potential on early-stage NPCs during the midgestation period, although the underlying mechanisms are not fully understood. Here we performed microarray analysis and compared expression profiles between control and HMGA2-overexpressed NPCs. Mouse neocortical neuroepithelial cells were isolated at embryonic day 11.5 and cultured as neurospheres for 9 days in vitro in the presence of fibroblast growth factor (FGF) 2 and epidermal growth factor (EGF). These cells were infected with control or HMGA2-expressing retrovirus, cultured in the presence of FGF and EGF for 3 days. Half of them were collected immediately for microarray analysis, and the other half were cultured in the absence of FGF for 12 h and then collected for microarray analysis.
2013-02-01 | E-GEOD-41882 | biostudies-arrayexpress
Project description:The culture of neural stem cells (NSCs) as floating neurospheres has become widely used as an experimental model to analyse the properties of NSCs. Although the neurosphere model has existed for two decades, there is still no standard protocol to grow NSCs in this way. Thus, we have analysed the consequences of the frequency of growth factor (FGF-2 and EGF) addition to embryonic and adult olfactory bulb stem cells (eOBSCs and aOBSCs) cultures, specifically in terms of proliferation, cell cycle progression, death and differentiation, as well as on global changes in gene expression and signaling pathways. We found that addition of FGF-2 and EGF every two or four days rather than daily significantly reduces the volume of the neurospheres and the total number of cells, changes that were more evident in aOBSC than in eOBSC cultures. The reduction in neurosphere size was mainly due to an increase in cell death and occurs without major changes in the cell cycle parameters tested. Moreover, partial deprivation of FGF-2 and EGF produces a mild increase in aOBSC differentiation during the proliferative phase. Remarkably, these effects were accompanied by a significant upregulation in the expression of genes involved in cell death regulation (Cryab), lipid catabolic processes (Pla2g7), cell adhesion (Dscaml1), cell differentiation (Dscaml1, Gpr17, S100b) and signal transduction (Gpr17, Ndrg2), among others. These findings support that continuous supply of FGF-2 and EGF is critical to maintain the viability/survival of NSCs in culture and reveals novel molecular hallmarks of NSC maintenance/survival and expansion in response to these growth factors. Total RNA was extracted from aOBSC cultures using the Trizol reagent (Invitrogen) and purified with Qiagen RNeasy Mini Kit separation columns (Qiagen). The RNA was sent to the Genomic Unit of CNB (Centro Nacional de Biotecnologia, Madrid, Spain). RNA integrity was corroborated by using Bioanalyzer. Then, cDNA was synthesized and hybridized to Affymetrix GeneChip Mouse Genome 430 2.0 arrays (Affymetrix, Santa Clara, CA, http://www.affymetrix.com) which contain a total of 45101 transcripts to assess and compare the overall gene expression profiles. 9 samples were analyzed. Ctr: Control mouse adult olfatory bulb stem cells (aOBSC) cultured with daily added Fgf2 and Egf, 3 biological rep C2: Mouse adult olfatory bulb stem cells (aOBSC) cultured with Fgf2 and Egf added every two days, 3 biological rep C4: Mouse adult olfatory bulb stem cells (aOBSC) cultured with Fgf2 and Egf added every four days, 3 biological rep
2012-04-26 | E-GEOD-37516 | biostudies-arrayexpress
Project description:Neural progenitor proliferation and cell fate decision from self-renewal to differentiation are crucial factors in determining brain size and morphology. The cytoskeletal dependent regulation of these processes is not entirely known. The actin-binding filamin A (FlnA) was shown to regulate proliferation of progenitors by directing changes in cell cycles proteins such as Cdk1 during G2/M phase. Here we report that functional loss of FlnA not only affects the rate of proliferation by altering cell cycle length but also causes a defect in early differentiation through changes in cell fate specification. FlnA interacts with Rho GTPase RhoA, and FlnA loss impairs RhoA activation. Disruption of either of these cytoskeletal associated proteins delays neurogenesis and promotes neural progenitors to remain in proliferative states. Aurora kinase B (Aurkb) has been implicated in cytokinesis, and peaks in expression during the G2/M phase. Inhibition of FlnA or RhoA impairs Aurkb degradation and alters its localization during mitosis. Overexpression of Aurkb replicates the same delay in neurogenesis seen with loss of FlnA or RhoA. Our findings suggest that shared cytoskeletal processes can direct neural progenitor proliferation by regulating the expression and localization of proteins that are implicated in the cell cycle progression and cell fate specification.
| S-EPMC6499011 | biostudies-literature
Project description:We performed genomic subtraction coupled to microarray-based gene expression profiling and identified the PDZ (postsynaptic density-95/Discs large/zona occludens-1)-binding kinase/T-LAK (lymphokine-activated killer T cell) cell originating protein kinase (PBK/TOPK) as a gene highly enriched in neural stem cell cultures. Previous studies have identified PBK/TOPK as a mitogen-activated protein kinase (MAPK) kinase that phosphorylated P38 MAPK but with no known expression or function in the nervous system. First, using a novel, bioinformatics-based approach to assess cross-correlation in large microarray datasets, we generated the hypothesis of a cell-cycle-related role for PBK/TOPK in neural cells. We then demonstrated that both PBK/TOPK and P38 are activated in a cell-cycle-dependent manner in neuronal progenitor cells in vitro, and inhibition of this pathway disrupts progenitor proliferation and self-renewal, a core feature of progenitors. In vivo, PBK/TOPK is expressed in rapidly proliferating cells in the adult subependymal zone (SEZ) and early postnatal cerebellar external granular layer. Using an approach based on transgenically targeted ablation and lineage tracing in mice, we show that PBK/TOPK-positive cells in the SEZ are GFAP negative but arise from GFAP-positive neural stem cells during adult neurogenesis. Furthermore, ablation of the adult stem cell population leads to concomitant loss of PBK/TOPK-positive cells in the SEZ. Together, these studies demonstrate that PBK/TOPK is a marker for transiently amplifying neural progenitors in the SEZ. Additionally, they suggest that PBK/TOPK plays an important role in these progenitors, and further implicates the P38 MAPK pathway in general, as an important regulator of progenitor proliferation and self-renewal.
| S-EPMC6725850 | biostudies-literature
Project description:The culture of neural stem cells (NSCs) as floating neurospheres has become widely used as an experimental model to analyse the properties of NSCs. Although the neurosphere model has existed for two decades, there is still no standard protocol to grow NSCs in this way. Thus, we have analysed the consequences of the frequency of growth factor (FGF-2 and EGF) addition to embryonic and adult olfactory bulb stem cells (eOBSCs and aOBSCs) cultures, specifically in terms of proliferation, cell cycle progression, death and differentiation, as well as on global changes in gene expression and signaling pathways. We found that addition of FGF-2 and EGF every two or four days rather than daily significantly reduces the volume of the neurospheres and the total number of cells, changes that were more evident in aOBSC than in eOBSC cultures. The reduction in neurosphere size was mainly due to an increase in cell death and occurs without major changes in the cell cycle parameters tested. Moreover, partial deprivation of FGF-2 and EGF produces a mild increase in aOBSC differentiation during the proliferative phase. Remarkably, these effects were accompanied by a significant upregulation in the expression of genes involved in cell death regulation (Cryab), lipid catabolic processes (Pla2g7), cell adhesion (Dscaml1), cell differentiation (Dscaml1, Gpr17, S100b) and signal transduction (Gpr17, Ndrg2), among others. These findings support that continuous supply of FGF-2 and EGF is critical to maintain the viability/survival of NSCs in culture and reveals novel molecular hallmarks of NSC maintenance/survival and expansion in response to these growth factors. Total RNA was extracted from aOBSC cultures using the Trizol reagent (Invitrogen) and purified with Qiagen RNeasy Mini Kit separation columns (Qiagen). The RNA was sent to the Genomic Unit of CNB (Centro Nacional de Biotecnologia, Madrid, Spain). RNA integrity was corroborated by using Bioanalyzer. Then, cDNA was synthesized and hybridized to Affymetrix GeneChip Mouse Genome 430 2.0 arrays (Affymetrix, Santa Clara, CA, http://www.affymetrix.com) which contain a total of 45101 transcripts to assess and compare the overall gene expression profiles.
2012-04-27 | GSE37516 | GEO
Project description:Gliomas have been proposed to be driven by a population of neural stem-like cells. We isolated a panel of novel human glioma cell lines using adherent neural stem cell conditions. The normal human foetal (hf) NS cells and the tumorigenic glioma NS cell lines were expanded using growth factors EGF and FGF in adherent culture conditions. In these conditions apoptosis and differentiation are suppressed resulting in more homogeneous populations of stem cells than has been reported previously. We included parallel primary biopsies of non-malignant brain tissue ('Normal Brain').
2009-03-13 | GSE15209 | GEO
Project description:The neural crest arises at the border between the neural plate and the adjacent non-neural ectoderm. It has been suggested that both neural and non-neural ectoderm can contribute to the neural crest. Several studies have examined the molecular mechanisms that regulate neural crest induction in neuralized tissues or the neural plate border. Here, using the chick as a model system, we address the molecular mechanisms by which non-neural ectoderm generates neural crest. We report that in response to FGF the non-neural ectoderm can ectopically express several early neural crest markers (Pax7, Msx1, Dlx5, Sox9, FoxD3, Snail2, and Sox10). Importantly this response to FGF signaling can occur without inducing ectopic mesodermal tissues. Furthermore, the non-neural ectoderm responds to FGF by expressing the prospective neural marker Sox3, but it does not express definitive markers of neural or anterior neural (Sox2 and Otx2) tissues. These results suggest that the non-neural ectoderm can launch the neural crest program in the absence of mesoderm, without acquiring definitive neural character. Finally, we report that prior to the upregulation of these neural crest markers, the non-neural ectoderm upregulates both BMP and Wnt molecules in response to FGF. Our results provide the first effort to understand the molecular events leading to neural crest development via the non-neural ectoderm in amniotes and present a distinct response to FGF signaling.
| S-EPMC3541687 | biostudies-literature
Project description:Comparison of genomic data from astrocytes and non-astrocyte cells from mice with or without FGF+EGF after SCI. We conducted genome-wide RNA sequencing of (i) immunoprecipitated astrocyte-specific ribosome-associated RNA (ramRNA) and (ii) the non-precipitated (flow-through) RNA deriving from non-astrocyte cells, from spinal cord tissue of mice recieving i) SCI alone, ii) SCI+hydrogel depot containing FGF+EGF, or iii) SCI+empty hydrogel depot.
2018-09-20 | GSE111529 | GEO
Project description:Background: Striatum is the crucial unit in brain involved in higher-level organizational learning, motor control and cognitive finctions. It also produces dopaminergic neurons, which play an important role in the control of multiple brain functions including voluntary movement and a span of neurobehavioral processes such as, mood, reward, addiction, and stress. Traumatic brain injury (TBI) lead to striatum related persistent cognitive dysfunctions. A number of cell based therapies such as; induced pluripotent stem cells (ips), neural stem cells (NSCs) and mesenchymal stem cells (MSCs), have been investigated so far for their potential application in TBI. But the journey from bench-to-bedside has not yet been covered sucessfully. As their survival and long-term maintenance in vivo has been huddle so far. So to understand the fate of embryonic striatal stem cells (ESSCs) in long-term neurogenesis in vitro, we have studied the neurogenic potential of rat embryonic striatal stem cells from E18th day embryos under conditioned microenvironments. Objectives: To evaluate the neuro-regenerative potential striatum-derived stem cells, we have employed synergestic effects of certain neurotrophins, such as ; EGF, IGF, FGF and LIF as in four combinations (Control/untreated-A, EGF+FGF-B, EGF+FGF+LIF-C, EGF+FGF+IGF-D and EGF+FGF+ IGF +LIF –E) in the microenvironment . To decipher the regulatory miRNAs involved in ESSC-derived neurogenesis, we have performed detailed miRNA profiling for ESSCs at passage 3 for groupD and group E derived ESSCs (based on their performance in vitro). Out data has explored cruicial mIRNAs involved in strital neurogenesis .
2011-08-25 | GSE30276 | GEO