Genome-wide analysis of HL60 cells after 24h pulse of 10nM vincristine
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE49869 | GEO | 2013/08/15
SECONDARY ACCESSION(S): PRJNA215198
REPOSITORIES: GEO
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Project description:Analysis of HL60 response to low-dose vincristine at gene expression level. The hypothesis tested in the present study was that population heterogeneity has functional consequences in drug response. Since the presence of discrete efflux^High and efflux^Low subpopulations may reflect transitions between distinct stable cellular states (attractor states), we measured the transcriptomes when the cell population exhibited a stable bimodal distribution. We also measured the transcriptomes for 17 days after washing the drug (samples 5 - 9). Total RNA obtained from HL60 cells untreated (sample 3), treated for 24h (sample 4) and sorted after 24h treatment for Calcein AM efflux low (sample 1) and high (sample 2). Sample 5 corresponds to total RNA of untreated cells, sample 6 to total RNA after 24h treatment with 10nM vincristine and samples 7 to 9 to total RNA after washing the drug.
2013-08-15 | E-GEOD-49869 | biostudies-arrayexpress
Project description:During commitment of a multipotent stem or progenitor cell to a particular lineage, a large number of genes alter their expression in a coordinated manner orchestrated by the gene regulatory network (GRN). The constraints imposed by the GRN govern how cells move in the high-dimensional gene expression state space and can be understood as a dynamical system in which phenotypic cell states (cell types) are attractors that stabilize the cell-type characteristic gene expression pattern against molecular noise. Despite insights from various theoretical models, it remains elusive how multipotent cells, when committing to a specific lineage, exit their attractor and enter a new distinct attractor. Here we show, using single-cell resolution monitoring of transcript patterns by qPCR that commitment of multipotent blood progenitor cells to either the erythroid or the myeloid lineage is preceded by a destabilization of the progenitorsâ?? attractor state and a slowing-down of relaxation of cells from outlier states, indicating a critical state transition (â??tipping pointâ??). The high-dimensionality of the system (many genes) and availability of individual trajectories of a large ensemble of systems (many cells) affords a novel signature for critical transition which can be predicted from theory: Decrease of correlation between cells and concomitant increase of correlation between genes as the cell population approaches the tipping point. Consistent with a destabilizing bifurcation that simultaneously opens access to the erythroid and myeloid attractors, differentiation signal for either lineage caused some cells to commit to the â??wrongâ?? fate; moreover providing conflicting signals resulted in a delayed decision at the bifurcation point that however was ultimately resolved by commitment to one fate. These results suggest that the theoretical framework of â??early-warning signsâ?? and critical transitions can be applied to ensembles of high-dimensional systems, offering a formal tool for analyzing single-cell omics data beyond current descriptive computational pattern recognition. Mouse blood progenitor cells (EML cell line) was exposed to EPO, IL-3/GM-CSF or a mixture of both cytokines and gene expression change was measured in sorted subpopulations wrt Sca1 progenitor surface marker expression. In total, there was 4 conditions (including control), three time points (including d0) and 20 samples (10 samples in duplicates) were analyzed. Two independent experiments were performed for each condition. The untreated progenitor cell population was used as control.
2016-09-01 | E-GEOD-70405 | biostudies-arrayexpress
Project description:Using the HL60 multipotent promyelocytic leukemia cell line, we performed experiments that lead to two different cell fate attractors by treatments of varying dosage and duration of the differentiation agent all-trans-retinoic acid (ATRA). The dosage and duration combinations corresponding to the two treatments were chosen by means of of cytometric measurements of CD11b, a well-known early differentiation marker, such that the two populations are poised at the same stage of differentiation. Using the selected treatment combinations, one population proceeds toward the terminally differentiated neutrophil attractor while the other population reverts back toward the undifferentiated promyelocytic attractor. We monitored the gene expression changes in the two populations after their respective treatments over a period of five days and identified a set of genes that diverged in their expression; a subset of which promotes neutrophil differentiation while the other represses cell cycle progression. By employing promoter based transcription factor binding site analysis, we found enrichment of transcription factors functionally linked to tumor progression, cell cycle, and development. Keywords: Time course, dose response Untreated HL60 cells are hybrized on the channel 1 with Cy3, ATRA-Treated HL60 cells are hybridized on channel 2 with Cy5. HK60 cells were treated with high dosage/short duration and low dosage/long duration to achieve 55% of CD11b+ cells. These positive cells were then isolated and culture in fresh media and total RNA were isolated for comparison. Cells treated with high dosage/short duration treatment proceed toward the neutrophil attractor while cells treated with the low dosage/long duration treatment revert back toward the promyelocyte attractor.
2008-11-19 | E-GEOD-13673 | biostudies-arrayexpress
Project description:Drug efflux is a common resistance mechanism found in bacteria and cancer cells. Although several structures of drug efflux pumps are available, they provide only limited functional information on the phenomenon of drug efflux. Here, we performed deep mutational scanning (DMS) on the bacterial ATP binding cassette (ABC) transporter EfrCD from Enterococcus faecalis to determine the drug efflux activity profile of more than 1400 single variants
2021-11-25 | GSE189399 | GEO
Project description:To confirm how many and what kind of gene changes within 1 hour treatment of insulin stimulation, we have performed whole genome microarray expression profiling. And we found that 276 genes increased (>2 fold) or decreased (<0.5 fold) 10nM insulin induced gene expression in Fao cells was measured at 0, 15, 30, 45, 60 min.
2014-07-01 | E-GEOD-58302 | biostudies-arrayexpress
Project description:During commitment of a multipotent stem or progenitor cell to a particular lineage, a large number of genes alter their expression in a coordinated manner orchestrated by the gene regulatory network (GRN). The constraints imposed by the GRN govern how cells move in the high-dimensional gene expression state space and can be understood as a dynamical system in which phenotypic cell states (cell types) are attractors that stabilize the cell-type characteristic gene expression pattern against molecular noise. Despite insights from various theoretical models, it remains elusive how multipotent cells, when committing to a specific lineage, exit their attractor and enter a new distinct attractor. Here we show, using single-cell resolution monitoring of transcript patterns by qPCR that commitment of multipotent blood progenitor cells to either the erythroid or the myeloid lineage is preceded by a destabilization of the progenitors’ attractor state and a slowing-down of relaxation of cells from outlier states, indicating a critical state transition (“tipping point”). The high-dimensionality of the system (many genes) and availability of individual trajectories of a large ensemble of systems (many cells) affords a novel signature for critical transition which can be predicted from theory: Decrease of correlation between cells and concomitant increase of correlation between genes as the cell population approaches the tipping point. Consistent with a destabilizing bifurcation that simultaneously opens access to the erythroid and myeloid attractors, differentiation signal for either lineage caused some cells to commit to the “wrong” fate; moreover providing conflicting signals resulted in a delayed decision at the bifurcation point that however was ultimately resolved by commitment to one fate. These results suggest that the theoretical framework of “early-warning signs” and critical transitions can be applied to ensembles of high-dimensional systems, offering a formal tool for analyzing single-cell omics data beyond current descriptive computational pattern recognition.
2016-09-01 | GSE70405 | GEO
Project description:This study investigated the effect of milbemycons as efflux inhibitors and antifungal agents. Milbemycin oxims can inhibit growth of Candida glabrata and C. albicans. The effect of milbemycins on transcriptomes was inbvestigated. Gene expression was measured in C. glabrata milbemycin-treated cells (1h) and compared to untreated cells in the incubation mediun RPMI. The one-color system was used. Four biological replicates were used for each condition. Gene expression was measured in C. albicans milbemycin-treated cells (1h) and compared to untreated cells in the incubation mediun RPMI. The one-color system was used. Three biological replicates were used for each condition.
2013-03-08 | E-GEOD-40232 | biostudies-arrayexpress
Project description:Expression of efflux pumps is a key feature of most cells which are resistant to multiple antibiotics. This study used TraDIS-Xpress, a genome wide transposon mutagenesis technology to identify genes in Escherichia coli and Salmonella Typhimurium involved in drug efflux and its regulation. We exposed mutant libraries to the canonical efflux substrate acriflavine in the presence and absence of the efflux inhibitor phenylalanine-arginine β-naphthylamide. Comparisons between conditions identified efflux specific and drug specific responses. Known efflux associated genes were easily identified including: AcrAB-TolC, MarA, RamA and SoxS confirming specificity of the response. Further genes encoding cell envelope maintenance enzymes and products involved with stringent response activation, DNA housekeeping, respiration and glutathione biosynthesis were also identified as affecting efflux activity in both species. We identified a conserved set of pathways crucial for efflux activity in these experimental conditions which expands the list of genes known to impact efflux efficacy.
2022-11-12 | E-MTAB-12353 | biostudies-arrayexpress
Project description:The identification of multidrug resistant (MDR), extensively and totally drug resistant Mycobacterium tuberculosis (Mtb), in vulnerable sites such as Mumbai, is a grave threat to the control of tuberculosis. The current study aimed at explaining the rapid expression of MDR in Directly Observed Treatment Short Course (DOTS) compliant patients, represents the first study comparing global transcriptional profiles of 3 pairs of clinical Mtb isolates, collected longitudinally at initiation and completion of DOTS. While the isolates were drug susceptible (DS) at onset and MDR at completion of DOTS, they exhibited identical DNA fingerprints at both points of collection. The whole genome transcriptional analysis was performed using total RNA from H37Rv and 3 locally predominant spoligotypes viz. MANU1, CAS and Beijing, hybridized on MTBv3 (BuG@S) microarray, and yielded 36, 98 and 45 differentially expressed genes respectively. Genes encoding transcription factors (sig, rpoB), cell wall biosynthesis (emb genes), protein synthesis (rpl) and additional central metabolic pathways (ppdK, pknH, pfkB) were found to be down regulated in the MDR isolates as compared to the DS isolate of the same genotype. Up regulation of drug efflux pumps, ABC transporters, trans-membrane proteins and stress response transcriptional factors (whiB) in the MDR isolates was observed. The data indicated that Mtb, without specific mutations in drug target genes may persist in the host due to additional mechanisms like drug efflux pumps and lowered rate of metabolism. Furthermore this population of Mtb, which also showed reduced DNA repair activity, would result in selection and stabilization of spontaneous mutations in drug target genes, causing selection of a MDR strain in the presence of drug pressures. Efflux pump such as drrA may play a significant role in increasing fitness of low level drug resistant cells and assist in survival of Mtb till acquisition of drug resistant mutations with least fitness cost. [Data is also available from http://bugs.sgul.ac.uk/E-BUGS-134]
2013-04-24 | E-BUGS-134 | biostudies-arrayexpress
Project description:Background: Atherosclerosis (AS)-associated cardiovascular disease is an important cause of mortality in an aging population of people living with HIV (PLWH). This elevated risk of atherosclerosis has been attributed to viral infection, prolonged usage of anti-retroviral therapy, and subsequent chronic inflammation. Methods: To investigate dysregulated immune signaling in PLWH with and without AS, we sequenced 9368 peripheral blood mononuclear cells (PBMCs) from 8 PLWH, 4 of whom also had atherosclerosis (AS+). To develop executable models of signaling pathways that drive cellular states in HIV-associated atherosclerosis, we developed the single-cell Boolean Omics Network Invariant Time Analysis (scBONITA) algorithm. ScBONITA (a) uses single-cell RNA sequencing data to infer Boolean rules for topologically characterized networks, (b) prioritizes genes based on their impact on signaling, (c) performs pathway analysis, and (d) maps sequenced cells to characteristic signaling states. We used scBONITA to identify dysregulated pathways in different cell-types from AS+ PLWH and AS- PLWH. To compare our findings with pathways associated with HIV infection, we used scBONITA to analyze a publicly available dataset of PBMCs from subjects before and after HIV infection. Additionally, the executable Boolean models characterized by scBONITA were used to analyze observed cellular states corresponding to the steady states of signaling pathways Results: We identified an increased subpopulation of CD8+ T cells and a decreased subpopulation of monocytes in AS+ PLWH. Dynamic modeling of signaling pathways and pathway analysis with scBONITA provided a new perspective on the mechanisms of HIV-associated atherosclerosis. Lipid metabolism and cell migration pathways are induced by AS rather than by HIV infection. These pathways included AGE-RAGE and PI3K-AKT signaling in CD8+ T cells, and glucagon and cAMP signaling pathways in monocytes. Further analysis of other cell subpopulations suggests that the highly interconnected PI3K-AKT signaling pathway drives cell migratory state in response to dyslipidemia. scBONITA attractor analysis mapped cells to pathway-specific signaling states that correspond to distinct cellular states. Conclusions: Dynamic network modeling and pathway analysis with scBONITA indicates that dysregulated lipid signaling regulates cell migration into the vascular endothelium in AS+ PLWH. Attractor analysis with scBONITA facilitated pathway-based characterization of cellular states that are not apparent in gene expression analyses.
2022-09-06 | GSE198339 | GEO