Homo sapiens
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-50572
PROVIDER: PRJNA217965 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Gene signature of CLL cells cultured with activated T cells or CD40L-expressing cells
2025-01-24 | E-GEOD-50572 | ExpressionAtlas
Project description:Chronic Lymphocytic Leukemia (CLL) cells multiply in secondary lymphoid tissue but the mechanisms leading to their proliferation are still uncertain. In addition to BCR-triggered signals, other microenvironmental factors might well be involved. In proliferation centres, leukemic B cells are in close contact with CD4+CD40L+ T cells. Therefore, we here dissected the signals provided by autologous activated T cells (Tact) to CLL cells. Although the gene expression profile induced by Tact was highly similar to that induced by sole CD40 signaling, an obvious difference was that Tact induced proliferation of CLL cells. We determined that stimulation with only CD40L+IL-21 was sufficient to induce robust proliferation in CLL cells. We then defined an IL-21-induced gene signature in CLL, containing components of JAK-STAT and apoptosis pathways, and this signature could be detected in lymph node (LN) samples from patients. Finally, we could detect IL-21 RNA and protein in LN, and IL-21 production ex vivo by LN CD4+CXCR5+ follicular helper T cells. These results indicate that, in addition to BCR signaling, activated T cells might contribute to CLL cell proliferation via CD40 and IL-21. Targeting these signaling pathways might offer new venues for treatment of CLL. CLL cells were cultured under different conditions for 16 hours and then sorted to purity as CD20+ CD5+ cells.
2013-10-07 | E-GEOD-50572 | biostudies-arrayexpress
Project description:Chronic Lymphocytic Leukemia (CLL) cells multiply in secondary lymphoid tissue but the mechanisms leading to their proliferation are still uncertain. In addition to BCR-triggered signals, other microenvironmental factors might well be involved. In proliferation centres, leukemic B cells are in close contact with CD4+CD40L+ T cells. Therefore, we here dissected the signals provided by autologous activated T cells (Tact) to CLL cells. Although the gene expression profile induced by Tact was highly similar to that induced by sole CD40 signaling, an obvious difference was that Tact induced proliferation of CLL cells. We determined that stimulation with only CD40L+IL-21 was sufficient to induce robust proliferation in CLL cells. We then defined an IL-21-induced gene signature in CLL, containing components of JAK-STAT and apoptosis pathways, and this signature could be detected in lymph node (LN) samples from patients. Finally, we could detect IL-21 RNA and protein in LN, and IL-21 production ex vivo by LN CD4+CXCR5+ follicular helper T cells. These results indicate that, in addition to BCR signaling, activated T cells might contribute to CLL cell proliferation via CD40 and IL-21. Targeting these signaling pathways might offer new venues for treatment of CLL.
2013-10-07 | GSE50572 | GEO
Project description:In this experiment we in vitro activated CLL cells on a layer of fibroblasts expressing CD40L (3T40) or nothing (3T3) for 48 hours. After the 48 hours, cells were taken off the fibroblasts and sorted for viable CD19+ cells. Then we performed RNA sequencing.
2022-05-20 | GSE201341 | GEO
Project description:In this experiment we in vitro activated CLL cells on a layer of fibroblasts expressing CD40L (3T40) in the presence of 100 nM Dasatinib for 48 hours. After the 48 hours, cells were taken off the fibroblasts and sorted for viable CD19+ cells. Then we performed RNA sequencing.
2024-05-01 | GSE264554 | GEO
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
2010-09-25 | GSE24338 | GEO
Project description:The retention and re-migration of Chronic Lymphocytic Leukemia cells into cytoprotective and proliferative lymphoid niches is thought to contribute to the development of resistance leading to subsequent disease relapse. The aim of this study was to elucidate the molecular processes that govern CLL cell migration to elicit a more complete inhibition of tumor cell migration. We compared the phenotypic and transcriptional changes induced in CLL cells using two distinct models designed to recapitulate the peripheral circulation, CLL cell migration across an endothelial barrier and the lymph node interaction between CLL cells and activated T cells. Initially, CLL cells were co-cultured with CD40L-expressing fibroblasts and exhibited an activated B-cell phenotype and their transcriptional signatures demonstrated the upregulation of pro-survival and anti-apoptotic genes and overrepresentation of the NF-κB signaling pathway. Using our dynamic circulating model we were able to study the transcriptomics and miRNomics associated with CLL migration. More than 3000 genes were altered when CLL cells underwent transendothelial migration, with overrepresentation of adhesion and cell migration gene sets. From this analysis an upregulation of the FAK signaling pathway was observed. Importantly, ptk2 (FAK) gene expression was significantly upregulated in migrating CLL cells (ptk2 Fold-change= 5.0). Here we demonstrate that TLR9 agonism increased levels of p-FAK (p<0.05) which could be prevented by pharmacological inhibition of FAK with defactinib (p<0.01). Furthermore, a reduction in CLL cell migration and invasion was observed when FAK was inhibited (p<0.05), supporting a role for FAK in both CLL migration and tissue invasion. Taken together, our data highlights the potential for combining FAK inhibition with current targeted therapies as a more effective treatment regime for CLL.
2022-03-22 | GSE198455 | GEO
Project description:The retention and re-migration of Chronic Lymphocytic Leukemia cells into cytoprotective and proliferative lymphoid niches is thought to contribute to the development of resistance leading to subsequent disease relapse. The aim of this study was to elucidate the molecular processes that govern CLL cell migration to elicit a more complete inhibition of tumor cell migration. We compared the phenotypic and transcriptional changes induced in CLL cells using two distinct models designed to recapitulate the peripheral circulation, CLL cell migration across an endothelial barrier and the lymph node interaction between CLL cells and activated T cells. Initially, CLL cells were co-cultured with CD40L-expressing fibroblasts and exhibited an activated B-cell phenotype and their transcriptional signatures demonstrated the upregulation of pro-survival and anti-apoptotic genes and overrepresentation of the NF-κB signaling pathway. Using our dynamic circulating model we were able to study the transcriptomics and miRNomics associated with CLL migration. More than 3000 genes were altered when CLL cells underwent transendothelial migration, with overrepresentation of adhesion and cell migration gene sets. From this analysis an upregulation of the FAK signaling pathway was observed. Importantly, ptk2 (FAK) gene expression was significantly upregulated in migrating CLL cells (ptk2 Fold-change= 5.0). Here we demonstrate that TLR9 agonism increased levels of p-FAK (p<0.05) which could be prevented by pharmacological inhibition of FAK with defactinib (p<0.01). Furthermore, a reduction in CLL cell migration and invasion was observed when FAK was inhibited (p<0.05), supporting a role for FAK in both CLL migration and tissue invasion. Taken together, our data highlights the potential for combining FAK inhibition with current targeted therapies as a more effective treatment regime for CLL.
2022-03-22 | GSE198454 | GEO
Project description:The retention and re-migration of Chronic Lymphocytic Leukemia cells into cytoprotective and proliferative lymphoid niches is thought to contribute to the development of resistance leading to subsequent disease relapse. The aim of this study was to elucidate the molecular processes that govern CLL cell migration to elicit a more complete inhibition of tumor cell migration. We compared the phenotypic and transcriptional changes induced in CLL cells using two distinct models designed to recapitulate the peripheral circulation, CLL cell migration across an endothelial barrier and the lymph node interaction between CLL cells and activated T cells. Initially, CLL cells were co-cultured with CD40L-expressing fibroblasts and exhibited an activated B-cell phenotype and their transcriptional signatures demonstrated the upregulation of pro-survival and anti-apoptotic genes and overrepresentation of the NF-κB signaling pathway. Using our dynamic circulating model we were able to study the transcriptomics and miRNomics associated with CLL migration. More than 3000 genes were altered when CLL cells underwent transendothelial migration, with overrepresentation of adhesion and cell migration gene sets. From this analysis an upregulation of the FAK signaling pathway was observed. Importantly, ptk2 (FAK) gene expression was significantly upregulated in migrating CLL cells (ptk2 Fold-change= 5.0). Here we demonstrate that TLR9 agonism increased levels of p-FAK (p<0.05) which could be prevented by pharmacological inhibition of FAK with defactinib (p<0.01). Furthermore, a reduction in CLL cell migration and invasion was observed when FAK was inhibited (p<0.05), supporting a role for FAK in both CLL migration and tissue invasion. Taken together, our data highlights the potential for combining FAK inhibition with current targeted therapies as a more effective treatment regime for CLL.
2022-03-22 | GSE198453 | GEO
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.
2011-02-19 | GSE20463 | GEO