Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

75 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptional response in acute lymphoblastic leukaemia cells to bone marrow microenvironment

ABSTRACT: Glucocorticoids (GCs) and topoisomerase II inhibitors are used in the treatment of acute lymphoblastic leukaemia (ALL) due to their ability to induce cell death in lymphoid cells. GC-induced apoptosis is mediated by the glucocorticoid receptor (GR), whereas topoisomerase II inhibitors cause DNA damage and activate sensors of DNA damage including the tumour suppressor p53. In order to shed light on the role of the microenvironment in cell death and identify determinants of drug sensitivity we performed transcriptomic analysis in ALL cells treated with the synthetic glucocorticoid dexamethasone, and the topoisomerase II inhibitor etoposide combined with bone marrow-derived conditioned media (CM).

ORGANISM(S): Homo sapiens

SUBMITTER: Leo Zeef

PROVIDER: E-MTAB-4761 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Lsd1 coordinates trophoblast development by retaining stem cells in their niche and directing cell fate

Project description:Stem cells reside in specific niches providing stemness-maintaining environments. Thus, the regulated migration from these niches is associated with differentiation onset. However, mechanisms retaining stem cells in their niche remain poorly understood. Here, we show that the epigenetic regulator lysine-specific demethylase 1 (Lsd1) organises the trophoblast niche of the early mouse embryo by coordinating migration and invasion of trophoblast stem cells (TSCs). Lsd1 deficiency leads to the depletion of the stem cell pool resulting from precocious migration of TSCs. Migration is induced by premature expression of the transcription factor Ovol2 that is repressed by Lsd1 in undifferentiated wild-type TSCs. Increasing Ovol2 levels suffices to recapitulate the migration phenotype. Furthermore, Lsd1-deficient TSCs exhibit a developmental bias towards cells of the syncytiotrophoblast and impaired spongiotrophoblast and trophoblast giant cell differentiation. In summary, we describe that the epigenetic modifier Lsd1 coordinates placental development by retaining TSCs in their niche and directing trophoblast differentiation. Mouse trophoblast stem cells (TSCs) were isoloated from a single conditional Lsd1-deficient mouse (Lsd1tm1SchM-CM-<le). Deletion of Lsd1 was induced eight days before the collection of RNA by addition of 0.2 M-BM-5M 4OH-tamoxife. Cells were isolated at successive stages of differentiation for total RNA extraction and hybridization on Affymetrix microarrays. To that end, we harvested cells at three time-points: before induction of differentiation (d0), two days after induction of differentiation (d2), and four days after induction of differentiation (d4). Three replicates (1, 2, 3) for control (-) and Lsd1-deficeint (+) cells were included for each differentiation stage.

2014-01-17 | E-GEOD-38277 | biostudies-arrayexpress

An Invasive Gene Expression Signature in Pancreas Cancer

Project description:Gene expression profiling has demonstrated clinical utility as a predictive tool in clinical oncology. We have identified genes associated with invasion of pancreatic cancer, and with potential for identifying early recurrence. We used Affymetrix Human U133 Plus 2.0 microarrays to identify specific predictive profiles in pancreatic cancer, and the evolution of gene expression. We identified distinct classes of up-regulated genes during this process. Primary and metastatic pancreatic cancer cell lines (BxPC-3 and AsPC-1), were stimulated with with phorbol-12-myristate 13-acetate (PMA), a known inducer of invasion. Affymetrix gene expression microarray analysis was performed, comparing PMA stimulated BxPC-3 and AsPC-1 gene expression to unstimulated controls, and also PMA stimulated BxPC-3 verses stimulated AsPC-1 cell lines. Differential gene expression was identified using ArrayAssist bioinformatics software. Gene expression changes were confirmed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) (Assays-on-demand, Taqman, ABI systems). Pathway Assist and GOstat were used to identify pathway and gene ontology changes.

2011-01-01 | E-GEOD-22973 | biostudies-arrayexpress

Pervasive Roles of Ubiquitination in Orchestrating the Deubiquitinase Activity and Function of the BAP1/ASXL2 Tumor Suppressor Complex

Project description:The tumor suppressor and deubiquitinase (DUB) BAP1 regulates chromatin-associated processes and is frequently mutated in various malignancies. BAP1 and its drosophila orthologue Calypso assemble DUB complexes with ASXL-1, -2, -3 paralogues and ASX respectively, and these cofactors are required for stimulating their DUB activity. However how the DUB activity of BAP1 is regulated remains largely unknown. Here we show that BAP1 promotes monoubiquitination of ASXLs on the ASXM/DEUBAD domain. ASXL2 monoubiquitination promotes its stability or proteasomal degradation, stimulates BAP1 DUB activity and is required for mammalian cell proliferation. Monoubiquitination of ASXL2 is directly catalyzed by UBE2E family of ubiquitin conjugating enzymes and is regulated by deubiquitination. Monoubiquitination of ASX is regulated by Calypso and is required for drosophila development. We further revealed a switch mechanism that tightly regulate BAP1 function, as a monoubiquitination of BAP1 UCH domain is mutually exclusive with ASXL2 monoubiquitination, thus ensuring highly coordinated DUB-mediated signaling.

2018-09-28 | PXD011124 | Pride

Paracrine activation of hCMEC/D3 cells by LPS-stimulated macrophages

Project description:Transcriptional profiling of hCMEC/D3 endothelial cells after six hour incubation with conditioned media from unstimulated or LPS-stimulated monocyte derived macrophages

2015-12-31 | E-MTAB-3692 | biostudies-arrayexpress

Glucocorticoid therapy regulates podocyte motility by inhibition of Rac1

Project description:Nephrotic syndrome (NS) occurs when the glomerular filtration barrier becomes excessively permeable leading to massive proteinuria. In childhood NS, dysregulation of the immune system has been implicated and increasing evidence points to the central role of podocytes in the pathogenesis. Children with NS are typically treated with an empiric course of glucocorticoid (Gc) therapy; a class of steroids that are activating ligands for the glucocorticoid receptor (GR) transcription factor. Although Gc-therapy has been the cornerstone of NS management for decades, the mechanism of action, and target cell, remain poorly understood. We tested the hypothesis that Gc acts directly on the podocyte to produce clinically useful effects without involvement of the immune system. In human podocytes, we demonstrated that the basic GR-signalling mechanism is intact and that Gc induced an increase in podocyte barrier function. To gain mechanistic insight we performed RNA microarray and ChIP-sequencing and identified Gc regulation of motility genes.

2017-07-17 | E-MTAB-5235 | biostudies-arrayexpress

Transcription profiling of mouse macrophages infected with Leishmania major or Leishmania donovani

Project description:Murine bone marrow derived macrophages were infected with Leishmania major or Leishmania donovania promastigotes, allowed to phagocytose latex beads or not treated. Gene expression profiles were compared to identify i) the effect of Leishmania infection; ii) the differences in effects between L. major and L. donovani; and iii) the effect of pahgocytosis of latex beads.

2008-02-05 | E-MEXP-1254 | biostudies-arrayexpress

FOX proteins exhibit overlapping and specific binding profiles to control gene expression

Project description:Transcription factors belonging to the same transcription factor families contain very similar DNA binding domains and hence have the potential to bind to related DNA sequences. However subtle differences in binding specificities can be detected in vitro with the potential to direct specific responses in vivo. In this study the binding properties of three Forkhead transcription factors, FOXK2, FOXO3 and FOXJ3 were studied in vivo. Here we submit the gene expression component of this study. LY294002 treatment of U2OS cells which promotes FOXO3 translocation to the nucleus, and hence activation of the FOXO3 target genes.

2016-01-20 | E-MTAB-3763 | biostudies-arrayexpress

PCNA has specific functions in regulation of metabolism in haematological cells

Project description:PCNA´s essential roles in DNA replication and repair are well established, while it’s recently discovered non-canonical roles in cellular signalling and regulation of metabolism are less explored. Recent data has indicated that PCNA has a specific non-canonical role in cells of haematological origin. In the present study we have explored this further at the system level by extensive protein-, gene expression, and metabolite profiling combined with integrated pathway analysis and by 13C label experimentation, Here we show that impairing PCNA´s scaffold functions led to massive changes in cellular signalling, but more importantly, a strong reduction in glycolytic metabolites and nucleoside phosphate pools in haematological cancer cell lines was detected, including multiple myeloma cells and acute myelogen leukaemia cells. This was not observed in cell lines from solid tissues such as kidney, bladder and prostate, nor in primary monocytes. Lipopolysaccharide (LPS) stimulated monocytes on the other hand, responded to treatment similarly to the haematological cancer cells, suggesting that cellular stress is an important factor for the response to the APIM-peptide in haematological cells. Integrated Pathway analysis of the metabolite and protein datasets revealed that protein ubiquitination and antigen presentation pathways are affected in haematopoietic cancer cells upon treatment. Focusing on one multiple myeloma cell line we further verified these trends by gene-expression and show that the consequences of reduced central carbon metabolite pools and energy charge is impaired redox and HIF1A regulation. Altogether, our data suggests that PCNA has an important role in regulation of cytoplasmic stress via regulation of central carbon metabolism in haematological cells that can be targeted in cancer treatment.

2023-03-10 | PXD017474 | Pride

Deletion of GSE1 and HDAC1 inactivation alters proteomic profiles and cell cycle control

Project description:The DNA damage response (DDR) is orchestrated by multiple, tightly regulated signalling events. We discovered that genetic suppressor element 1 (GSE1) forms a complex with the histone deacetylation 1 (HDAC1) / CoREST complex and that loss of GSE1 hampers DDR induction. To investigate how GSE1 and HDAC1 can regulate DDR and whether their mode of action might be overlapping, we performed a proteomic analysis using quantitative mass spectrometry based on the TMTpro 16-plex isobaric labelling technology (Li et al., 2020). We determined global acetylome and phosphorylome profiles in the nearly haploid human cell line HAP1 (Andersson et al, 1987) using WT, GSE1 KO and HDAC1 CI backgrounds and compared patterns between untreated and etoposide-treated (0.1 µM, 6 hrs) cells.

2023-10-23 | PXD040339 | Pride

Impaired stability of tumor cells after targeting of lactate/pyruvate metabolism investigated by shotgun proteomics

Project description:Overexpression of heat shock proteins (HSPs), especially the major stress-inducible 72 kDa heat shock protein 70 (Hsp70), in malignant tumor cells is associated with therapeutic resistance. The heightened metabolic demand in tumor cells (Warburg effect) increases lactate dehydrogenase (LDH) activity and the corresponding increase in lactate concentrations promotes malignancy. Herein, we assessed the co-regulation of LDH and the heat shock response and its link to radiation resistance in B16F10 murine melanoma cells and LS174T human colorectal adenocarcinoma cells. Inhibition of LDHA/B by oxamate or GNE-140, significantly diminishes the expression of Hsp90, Hsp70 and Hsp27 in the cytosol. Diminished expression was also observed in LDHA/B double knockout (LDH-/-) cells. An increased production of reactive oxygen species (ROS) induced by a faster growth rate in wild type (WT) vs LDH-/- cells contributes to increased cytosolic HSP levels in WT cells. LDH-/- cells exhibit a lower density of membrane Hsp70 expression than WT cells and a decreased presence of the tumor-specific, Hsp70 anchoring glycosphingolipid Gb3 on the cell surface which could be attributed to an altered lipid metabolism mediated by the LDH knockout. Functionally, a double knockout of LDHA/B results in a generalized reduction in expression of HSPs in tumor cells and significantly increases radiosensitivity which is associated with a G2/M arrest. In summary, we demonstrate that pharmacological targeting of the lactate/pyruvate metabolism breaks radioresistance by impairing the stress response.

2022-02-17 | PXD026078 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data