Gene expression profiles of Glioblastoma stem cells in which ALK or pleiotrophin expression was suppressed
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Akiyama Tetsu
PROVIDER: S-ECPF-GEOD-32482 | biostudies-other |
REPOSITORIES: biostudies-other
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Project description:Cancer stem cells are believed to be responsible for tumor initiation and development. Much current research on human brain tumors is focused on the stem-like properties of glioblastoma stem cells. Anaplastic lymphoma kinase (ALK) and its ligand pleiotrophin are required for maintaining the stem-like properties and tumorigenicity of glioblastoma stem cells.
2011-10-01 | GSE32482 | GEO
Project description:Cancer stem cells are believed to be responsible for tumor initiation and development. Much current research on human brain tumors is focused on the stem-like properties of glioblastoma stem cells. Anaplastic lymphoma kinase (ALK) and its ligand pleiotrophin are required for maintaining the stem-like properties and tumorigenicity of glioblastoma stem cells. Human glioblastoma stem cells (GB2) were infected with a lentivirus expressing an shRNA targeting ALK or pleiotrophin.
2011-09-30 | E-GEOD-32482 | biostudies-arrayexpress
Project description:BackgroundUnderstanding the mechanisms controlling stem cell differentiation is the key to future advances in tissue and organ regeneration. Embryonic stem (ES) cell differentiation can be triggered by embryoid body (EB) formation, which involves ES cell aggregation in suspension. EB growth in the absence of leukaemia inhibitory factor (LIF) leads EBs to mimic early embryonic development, giving rise to markers representative of endoderm, mesoderm and ectoderm. Here, we have used microarrays to investigate differences in gene expression between 3 undifferentiated ES cell lines, and also between undifferentiated ES cells and Day 1-4 EBs.ResultsAn initial array study identified 4 gene expression changes between 3 undifferentiated ES cell lines. Tissue culture conditions for ES differentiation were then optimized to give the maximum range of gene expression and growth. -Undifferentiated ES cells and EBs cultured with and without LIF at each day for 4 days were subjected to microarray analysis. -Differential expression of 23 genes was identified. 13 of these were also differentially regulated in a separate array comparison between undifferentiated ES cells and compartments of very early embryos. A high degree of inter-replicate variability was noted when confirming array results. Using a panel of marker genes, RNA amplification and RT-PCR, we examined expression pattern variation between individual -D4-Lif EBs. We found that individual EBs selected from the same dish were highly variable in gene expression profile.ConclusionES cell lines derived from different mouse strains and carrying different genetic modifications are almost invariant in gene expression profile under conditions used to maintain pluripotency. Tissue culture conditions that give the widest range of gene expression and maximise EB growth involve the use of 20% serum and starting cell numbers of 1000 per EB. 23 genes of importance to early development have been identified; more than half of these are also identified using similar studies, thus validating our results. EBs cultured in the same dish vary widely in terms of their gene expression (and hence, undoubtedly, in their future differentiation potential). This may explain some of the inherent variability in differentiation protocols that use EBs.
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Project description:The aryl hydrocarbon receptor (AHR) is a ligand activated bHLH transcription factor that belongs to the Per-Arnt-Sim (PAS) superfamily of proteins involved in mediating responses to cellular environment regulating normal physiological and developmental pathways. The AHR binds a broad range of naturally derived and synthetic compounds, and plays a major role in mediating effects of certain environmental chemicals. Although our understanding of the physiological roles of the AHR in the immune system is evolving, there is little known about its role in hematopoiesis and hematopoietic diseases. Prior studies demonstrated that AHR null (AHR-KO) mice have impaired hematopoietic stem cell (HSC) function; they develop myeloproliferative changes in peripheral blood cells, and alterations in hematopoietic stem and progenitor cell populations in the bone marrow. We hypothesized mice lacking AHR expression only within hematopoietic cells (AHRVav1 mice) would develop similar changes. However, we did not observe a complete phenocopy of AHR-KO and AHRVav1 animals at 2 or 18 months of age. To illuminate the signaling mechanisms underlying the alterations in hematopoiesis observed in these mice, we sorted a population of cells highly enriched for HSC function (LSK cells: CD34-CD48-CD150+) and performed microarray analyses. Ingenuity Pathway and Gene Set Enrichment Analyses revealed that that loss of AHR within HSCs alters several gene and signaling networks important for HSC function. Differences in gene expression networks among HSCs from AHR-KO and AHRVav1 mice suggest that AHR in bone marrow stromal cells also contributes to HSC function. In addition, numerous studies have suggested a role for AHR in both regulation of hematopoietic cells, and in the development of blood diseases. More work is needed to define what these signals are, and how they act upon HSCs.
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Project description:Recently, a small population of cancer stem cells in adult and pediatric brain tumors has been identified. Some evidence has suggested that CD133 is a marker for a subset of leukemia and glioblastoma cancer stem cells. Especially, CD133 positive cells isolated from human glioblastoma may initiate tumors and represent novel targets for therapeutics. The gene expression and the drug resistance property of CD133 positive cancer stem cells, however, are still unknown.In this study, by FACS analysis we determined the percentage of CD133 positive cells in three primary cultured cell lines established from glioblastoma patients 10.2%, 69.7% and 27.5%, respectively. We also determined the average mRNA levels of markers associated with neural precursors. For example, CD90, CD44, CXCR4, Nestin, Msi1 and MELK mRNA on CD133 positive cells increased to 15.6, 5.7, 337.8, 21.4, 84 and 1351 times, respectively, compared to autologous CD133 negative cells derived from cell line No. 66. Additionally, CD133 positive cells express higher levels of BCRP1 and MGMT mRNA, as well as higher mRNA levels of genes that inhibit apoptosis. Furthermore, CD133 positive cells were significantly resistant to chemotherapeutic agents including temozolomide, carboplatin, paclitaxel (Taxol) and etoposide (VP16) compared to autologous CD133 negative cells. Finally, CD133 expression was significantly higher in recurrent GBM tissue obtained from five patients as compared to their respective newly diagnosed tumors.Our study for the first time provided evidence that CD133 positive cancer stem cells display strong capability on tumor's resistance to chemotherapy. This resistance is probably contributed by the CD133 positive cell with higher expression of on BCRP1 and MGMT, as well as the anti-apoptosis protein and inhibitors of apoptosis protein families. Future treatment should target this small population of CD133 positive cancer stem cells in tumors to improve the survival of brain tumor patients.
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