scholarly journals OPTC-2. Identification of enriched genes and pathways associated to hypoxia induced migration in patient-derived glioma stem cell lines by RNAseq

2021 ◽  
Vol 3 (Supplement_2) ◽  
pp. ii6-ii6
Author(s):  
Olivia Morris Hanon ◽  
Yamil Mahmoud ◽  
Mariana Vera ◽  
Romina Girotti ◽  
Gabriel Rabinovich ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Migratory Behavior ◽  
Pathway Enrichment Analysis ◽  
Glioma Stem Cell ◽  
Diffuse Infiltration ◽  
Stem Cell Lines ◽  
The Individual

Abstract Glioblastomas (GBM), the most prevalent and lethal primary brain tumors, are characterized by high intertumoral heterogeneity, diffuse infiltration, and resistance to conventional therapies. Notably, the ability of tumor cells to invade surrounding tissues is one of their most damaging characteristics, it not only causes resistance to therapies such as surgery and radiotherapy but is ultimately the primary cause of death. Therapies that cause hypoxia (e.g. anti-angiogenic therapies) have been shown to increase invasiveness, leading to resistance to the therapy itself and further complications for the patients. Using patient-derived glioma stem cell lines (GSCL) we have discovered cell lines that display heterogeneous migratory behavior in response to hypoxia. As expected we observed that four GSCLs studied had increased migration in hypoxia. Strikingly, two other cell lines studied showed decreased migration in hypoxia. This unforeseen result reflects the heterogeneous nature of GBM and the difference between these GSCLs could be key to understanding this variable. To delve into the molecular context that could explain these differences we performed an exploratory RNAseq analysis on four of the GSCLs, two that showed hypoxia-induced migration and two with decreased migration in hypoxia, and evaluated genes differentially expressed in hypoxia versus normoxia. We also carried out gene ontology and pathway enrichment analysis to discover molecular and pathway patterns consistent with the migratory behaviors observed in each group of GSCLs. The results show how that a similar migratory response to hypoxia coincides with particular sets of enriched genes and pathways. Specifically, we found NOTCH and WNT signaling pathways upregulated in GSCLs which showed increased migration in hypoxia while the IFN-gamma pathway upregulated in GSCLs with decreased migration in hypoxia. Knowing the individual molecular mechanisms responsible for the migratory behavior could allow for tailor-made therapies that reduce the dissemination of these tumors.

scholarly journals Secondary Data Analytics of Aquaporin Expression Levels in Glioblastoma Stem-Like Cells

2015 ◽  
Vol 14 ◽  
pp. CIN.S22058 ◽  
Author(s):  
Raphael D. Isokpehi ◽  
Katharina C. Wollenberg Valero ◽  
Barbara E. Graham ◽  
Maricica Pacurari ◽  
Jennifer N. Sims ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Lines ◽  
Data Analytics ◽  
Molecular Mechanisms ◽  
Function Analysis ◽  
Secondary Data ◽  
Tumor Formation ◽  
Stem Cell Marker ◽  
Glioma Stem Cell ◽  
Expression Levels

Glioblastoma is the most common brain tumor in adults in which recurrence has been attributed to the presence of cancer stem cells in a hypoxic microenvironment. On the basis of tumor formation in vivo and growth type in vitro, two published microarray gene expression profiling studies grouped nine glioblastoma stem-like (GS) cell lines into one of two groups: full (GSf) or restricted (GSr) stem-like phenotypes. Aquaporin-1 (AQP1) and aquaporin-4 (AQP4) are water transport proteins that are highly expressed in primary glial-derived tumors. However, the expression levels of AQP1 and AQP4 have not been previously described in a panel of 92 glioma samples. Therefore, we designed secondary data analytics methods to determine the expression levels of AQP1 and AQP4 in GS cell lines and glioblastoma neurospheres. Our investigation also included a total of 2,566 expression levels from 28 Affymetrix microarray probe sets encoding 13 human aquaporins (AQP0–AQP12); CXCR4 (the receptor for stromal cell derived factor-1 [SDF-1], a potential glioma stem cell therapeutic target]); and PROM1 (gene encoding CD133, the widely used glioma stem cell marker). Interactive visual representation designs for integrating phenotypic features and expression levels revealed that inverse expression levels of AQP1 and AQP4 correlate with distinct phenotypes in a set of cell lines grouped into full and restricted stem-like phenotypes. Discriminant function analysis further revealed that AQP1 and AQP4 expression are better predictors for tumor formation and growth types in glioblastoma stem-like cells than are CXCR4 and PROM1. Future investigations are needed to characterize the molecular mechanisms for inverse expression levels of AQP1 and AQP4 in the glioblastoma stem-like neurospheres.

scholarly journals Glioma Stem Cell Lines Expanded in Adherent Culture Have Tumor-Specific Phenotypes and Are Suitable for Chemical and Genetic Screens

2009 ◽  
Vol 4 (6) ◽  
pp. 568-580 ◽  
Author(s):  
Steven M. Pollard ◽  
Koichi Yoshikawa ◽  
Ian D. Clarke ◽  
Davide Danovi ◽  
Stefan Stricker ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Lines ◽  
Glioma Stem Cell ◽  
Genetic Screens ◽  
Adherent Culture ◽  
Stem Cell Lines

scholarly journals Delineating the Cytogenomic and Epigenomic Landscapes of Glioma Stem Cell Lines

PLoS ONE ◽  
2013 ◽  
Vol 8 (2) ◽  
pp. e57462 ◽  
Author(s):  
Simona Baronchelli ◽  
Angela Bentivegna ◽  
Serena Redaelli ◽  
Gabriele Riva ◽  
Valentina Butta ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Lines ◽  
Glioma Stem Cell ◽  
Stem Cell Lines

scholarly journals Neurosphere and adherent culture conditions are equivalent for malignant glioma stem cell lines

2015 ◽  
Vol 48 (1) ◽  
pp. 25 ◽  
Author(s):  
Maryam Rahman ◽  
Karina Reyner ◽  
Loic Deleyrolle ◽  
Sebastien Millette ◽  
Hassan Azari ◽  
...  
Keyword(s):  
Stem Cell ◽  
Malignant Glioma ◽  
Cell Lines ◽  
Culture Conditions ◽  
Glioma Stem Cell ◽  
Adherent Culture ◽  
Stem Cell Lines

scholarly journals Identification of Potential Key Genes and Pathways in Enzalutamide-Resistant Prostate Cancer Cell Lines: A Bioinformatics Analysis with Data from the Gene Expression Omnibus (GEO) Database

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Long Zheng ◽  
Xiaojie Dou ◽  
Xiaodong Ma ◽  
Wei Qu ◽  
Xiaoshuang Tang
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Gene Set Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Key Genes ◽  
Geo Database

Enzalutamide (ENZ) has been approved for the treatment of advanced prostate cancer (PCa), but some patients develop ENZ resistance initially or after long-term administration. Although a few key genes have been discovered by previous efforts, the complete mechanisms of ENZ resistance remain unsolved. To further identify more potential key genes and pathways in the development of ENZ resistance, we employed the GSE104935 dataset, including 5 ENZ-resistant (ENZ-R) and 5 ENZ-sensitive (ENZ-S) PCa cell lines, from the Gene Expression Omnibus (GEO) database. Integrated bioinformatics analyses were conducted, such as analysis of differentially expressed genes (DEGs), Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, protein-protein interaction (PPI) analysis, gene set enrichment analysis (GSEA), and survival analysis. From these, we identified 201 DEGs (93 upregulated and 108 downregulated) and 12 hub genes (AR, ACKR3, GPER1, CCR7, NMU, NDRG1, FKBP5, NKX3-1, GAL, LPAR3, F2RL1, and PTGFR) that are potentially associated with ENZ resistance. One upregulated pathway (hedgehog pathway) and seven downregulated pathways (pathways related to androgen response, p53, estrogen response, TNF-α, TGF-β, complement, and pancreas β cells) were identified as potential key pathways involved in the occurrence of ENZ resistance. Our findings may contribute to further understanding the molecular mechanisms of ENZ resistance and provide some clues for the prevention and treatment of ENZ resistance.

scholarly journals Noradrenaline Sensitivity Is Severely Impaired in Immortalized Adipose-Derived Mesenchymal Stem Cell Line

2018 ◽  
Vol 19 (12) ◽  
pp. 3712 ◽  
Author(s):  
Pyotr Tyurin-Kuzmin ◽  
Vadim Chechekhin ◽  
Anastasiya Ivanova ◽  
Daniyar Dyikanov ◽  
Veronika Sysoeva ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cell Lines ◽  
Adrenergic Receptor ◽  
Molecular Mechanisms ◽  
Single Cells ◽  
Receptor Expression ◽  
Embryonic Cells ◽  
Immortalized Cells ◽  
Stem Cell Lines

Primary adipose tissue-derived multipotent stem/stromal cells (adMSCs) demonstrate unusual signaling regulatory mechanisms, i.e., increased of sensitivity to catecholamines in response to noradrenaline. This phenomenon is called “heterologous sensitization”, and was previously found only in embryonic cells. Since further elucidation of the molecular mechanisms that are responsible for such sensitization in primary adMSCs was difficult due to the high heterogeneity in adrenergic receptor expression, we employed immortalized adipose-derived mesenchymal stem cell lines (hTERT-MSCs). Using flow cytometry and immunofluorescence microscopy, we demonstrated that the proportion of cells expressing adrenergic receptor isoforms does not differ significantly in hTERT-MSCs cells compared to the primary adMSCs culture. However, using analysis of Ca2+-mobilization in single cells, we found that these cells did not demonstrate the sensitization seen in primary adMSCs. Consistently, these cells did not activate cAMP synthesis in response to noradrenaline. These data indicate that immortalized adipose-derived mesenchymal stem cell lines demonstrated impaired ability to respond to noradrenaline compared to primary adMSCs. These data draw attention to the usage of immortalized cells for MSCs-based regenerative medicine, especially in the field of pharmacology.

scholarly journals Prospective stem cell lines as in vitro neurodegenerative disease models for natural product research

2019 ◽  
Vol 2 (1) ◽  
pp. 16-30
Author(s):  
Nur Izzati Mansor ◽  
Nuratiqah Azmi ◽  
King Hwa Ling ◽  
Rozita Rosli ◽  
Zurina Hassan ◽  
...  
Keyword(s):  
Natural Products ◽  
Stem Cell ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Vital Role ◽  
Common Source ◽  
Molecular Features ◽  
Natural Product Research ◽  
Stem Cell Lines

The use of in vitro model for screening pharmacological compounds or natural products has gained global interest.  The choice of cells to be manipulated plays a vital role in coming up with the best-suited model for specific diseases, including neurodegenerative diseases (ND). A good in vitro ND model should provide appropriate morphological and molecular features that mimic ND conditions where it can be used to screen potential properties of natural products in addition to unravelling the molecular mechanisms of ND.  In this mini review, we intend to demonstrate two prospective stem cell lines as the potential cell source for in vitro ND model and compare them to the commonly used cells.  The common source of cells that have been used as the in vitro ND models is discussed before going into details talking about the two prospective stem cell lines.

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