Filters
Technology
Platform
GSE75620
Homo sapiens
9 Downloadable Samples
Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
sorafenib is the treatment of reference for hepatocellular carcinoma (HCC). We applied sorafenib on the human HCC cell line Huh7 and the subclone shRb, carrying a stable knock-down of the expression of the RB1 gene, a key regulator of liver carcinogenesis. Our aim was to better understand the physiologic and metabolic consequences of the exposure of HCC cells to sorafenib.
Publication Title
Metallothionein-1 as a biomarker of altered redox metabolism in hepatocellular carcinoma cells exposed to sorafenib.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We have previously shown that Il1a-knockout (KO) mice exhibit rapid (at day 1) and persistent improvements in locomotion associated with reduced lesion volume compared with Il1b-KO mice and C57BL/6 controls after traumatic spinal cord injury (SCI). To investigate the mechanism by which Il1a mediates its detrimental effect, we analyzed the transcriptome of the injured spinal cord of Il1a-KO, Il1b-KO and C57BL/6 mice at 24 hours after SCI using GeneChip microarrays.
Publication Title
IL-1α Gene Deletion Protects Oligodendrocytes after Spinal Cord Injury through Upregulation of the Survival Factor Tox3.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Acute Myeloid Leukemia (AML) is frequently associated with mutations of NPM1 (NPM1c+) and even if considered to be of better prognosis for younger patients, relapse is frequent and outcome remains poor for elder patients with a need for novel treatment strategies. Differentiation-based therapy by all trans retinoic acid (ATRA) combined with arsenic trioxide (ATO) induce proteasomal degradation of NPM1c protein, NPM1 nuclear re localization, differentiation and apoptosis in NPM1c+ cells and blast clearance in relapsed/refractory AML patients. In line, the XPO1 inhibitor Selinexor showed similar results in vitro associated with down regulation of a specific HOX gene signature. BET inhibitors (BETi) OTX015 (MK-8628) and JQ1 yield antileukemic activity and here we demonstrate their effects in NPM1c+ leukemia cells compared to ATO+ATRA and Selinexor. Compared to ATO+ATRA and Selinexor, BRDi induced TP53 independent apoptosis, differentiation, proteasomal NPM1c degradation and nuclear relocalization in NPM1c+ OCI-AML3 cell line and to different extend in patient derived blast cells. As ATO+ATRA and Selinexor had significant biological activity in NPM1c+ cell line IMS-M2, these cells were resistant to BETi exposure, except for nuclear re localization of NPM1 which is a general phenomenon upon treatment with all three drug types. Gene profiling revealed that BRDi downregulate a BRD specific core gene signature in OCI-AML3 and IMS-M2 cells but IMS-M2 cells yield a transcriptional resistance signature including upregulation of the Wnt/beta-catenin pathway. HOX gene clusters in OCI-AML3 cells and IMS-M2 cells are heterogeneously regulated by BETi and are down regulated by ATO+ATRA in line with results reported for Selinexor treatment. Taken together, our preclinical results encourage clinical testing of ATO+ATRA, Selinexor and BRDi in NPM1c+ AML patients.
Publication Title
No associated publication
Sample Metadata Fields
Cell line, Compound
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Invariant natural killer T cells (iNKT) expressing the retinoic acid receptor-related orphan receptor γt (RORγt) and producing IL-17 represent a minor subset of CD1d-restricted iNKT cells (iNKT17) in C57BL/6J (B6) mice. We aimed in this study to define the reasons for their low distribution and the sequence of events accompanying their normal thymic development. We found that RORγt+ iNKT cells have higher proliferation potential and a greater propensity to apoptosis than RORγt- iNKT cells. These cells do not likely reside in the thymus indicating that thymus emigration, and higher apoptosis potential, could contribute to RORγt+ iNKT cell reduced thymic distribution. Ontogeny studies suggest that mature HSAlow RORγt+ iNKT cells might develop through developmental stages defined by a differential expression of CCR6 and CD138 during which RORγt expression and IL-17 production capabilities are progressively acquired. Finally, we found that RORγt+ iNKT cells perceive a strong TCR signal that could contribute to their entry into a specific Th17 like developmental program influencing their survival and migration. Overall, our study proposes a hypothetical thymic developmental sequence for iNKT17 cells, which could be of great use to study molecular mechanisms regulating this developmental program.
Publication Title
Characterization of the developmental landscape of murine RORγt+ iNKT cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 19 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Downregulation of Sfrp5 promotes beta cell proliferation during obesity in the rat.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The basic helix-loop-helix (bHLH) transcription factors of the Drosophilas atonal-related superfamily Neurogenin3 (Neurog3) and NeuroD1 promote endocrine differentiation in the gastrointestinal tract. Atonal Homolog 8 (Atoh8/Math6) is a newly identified member of the atonal-related family whose expression is induced by Neurog3 and NeuroD1 in cell culture, indicating a possible role for this gene in the endocrine differentiation program downstream of these two pro-endocrine factors. Intriguingly, available experimental evidence based on a reduced number of genes suggests that Atoh8 may negatively regulate Neurog3-targeting events. In this study, we have analyzed global changes in gene expression profiles upon exogenous expression of Atoh8 alone or in combination with Neurog3 in mouse pancreatic duct (mPAC) cells. These cells activate neuroendocrine-specific gene expression in response to Neurog3 and NeuroD1 and thus serve as an optimal model to evaluate the proendocrine activity of Atoh8. We have compared transcriptional profiles between mPAC cells treated with a recombinant adenovirus expressing Atoh8 (Ad-Atoh8) or a control adenovirus encoding B-galactosidase (Ad-Bgal), and between cells treated with Ad-Neurog3+Ad-Bgal or cells treated with Ad-Neurog3+Ad-Atoh8. The results obtained show that Atoh8 exhibits a very modest transcriptional activity in these cells thus confirming that Atoh8 does not function as a proendocrine gene. Furthermore, our data also confirm the ability of Atoh8 to block Neurog3-dependent transcriptional activation events. However, since repression is only seen for a small subset of Neurog3 gene targets, we discard a general role of Atoh8 as a negative regulator of Neurog3 pro-endocrine activity.
Publication Title
Characterization of the transcriptional activity of the basic helix-loop-helix (bHLH) transcription factor Atoh8.
Sample Metadata Fields
Cell line, Treatment
View Samples- Rattus norvegicus
- 11 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
Background and Aims: It is well demonstrated that in the beta cell population of the pancreas there is a dynamic turnover, which results from the net balance of several processes; beta cell replication, apoptosis and neogenesis. These processes have been studied in partial pancreatectomy and glucagon-like peptide 1 treated animals, where an increase in pancreas regeneration has been observed. Similarly, sodium tungstate, which decreases hyperglycemia in several animal models of diabetes, promotes a rise in the beta cell mass of nSTZ and STZ animals. However, the molecular mechanisms underlying this pancreas regeneration remain unknown. Therefore the objective of this study is to identify which genes are up or down regulated in the increase of the beta cell population of STZ rats treated with sodium tungstate.
Publication Title
Molecular mechanisms of tungstate-induced pancreatic plasticity: a transcriptomics approach.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 10 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Obesity is associated with an increase in -cell mass in response tothe rising demand for insulin. -cell plasticity is essential to maintaining glucose homeostasis, however,the cellular and molecular mechanisms by which -cell mass is regulated remain poorly understood.Recently, we described the existence of a crosstalk between the peripancreatic adipose tissue and -cells as a novel mechanism that participates in the regulation of -cell plasticity. Here, we identify the secreted frizzled-related protein (Sfrp) 5 as down-regulated in the pancreatic islets of obese rats as well as in the pancreatic islets of human obese patients. Our results demonstrate that the silencing of Sfrp5 induces an increase in -cell proliferation, which we correlate with the activation of Wnt signaling and of the MAPK and PI3 kinase pathways. Together, these findings expand our understanding of the mechanisms underlying -cell proliferation under conditions of obesity. Furthermore, this study opens new insights into the specific targeting of Sfrp5 as a novel therapeutic strategy for balancing -cell mass.
Publication Title
Downregulation of Sfrp5 promotes beta cell proliferation during obesity in the rat.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 9 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Obesity is associated with an increase in -cell mass in response tothe rising demand for insulin. -cell plasticity is essential to maintaining glucose homeostasis, however,the cellular and molecular mechanisms by which -cell mass is regulated remain poorly understood.Recently, we described the existence of a crosstalk between the peripancreatic adipose tissue and -cells as a novel mechanism that participates in the regulation of -cell plasticity. Here, we identify the secreted frizzled-related protein (Sfrp) 5 as down-regulated in the pancreatic islets of obese rats as well as in the pancreatic islets of human obese patients. Our results demonstrate that the silencing of Sfrp5 induces an increase in -cell proliferation, which we correlate with the activation of Wnt signaling and of the MAPK and PI3 kinase pathways. Together, these findings expand our understanding of the mechanisms underlying -cell proliferation under conditions of obesity. Furthermore, this study opens new insights into the specific targeting of Sfrp5 as a novel therapeutic strategy for balancing -cell mass.
Publication Title
Downregulation of Sfrp5 promotes beta cell proliferation during obesity in the rat.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Alterations in endoplasmic reticulum (ER) homeostasis have been implicated in the pathophysiology of obesity and type-2 diabetes (T2D). Acute ER stress induction in the hypothalamus produces glucose metabolism perturbations. However, the neurobiological basis linking hypothalamic ER stress with abnormal glucose metabolism remains unknown. Here we report that genetic and induced models of hypothalamic ER stress are associated with alterations in systemic glucose homeostasis due to increased gluconeogenesis (GNG) independent of body weight changes. Defective alpha melanocyte-stimulating hormone (a-MSH) production underlies this metabolic phenotype, as pharmacological strategies aimed at rescuing hypothalamic a-MSH content reversed this phenotype at metabolic and molecular level. Collectively, our results posit defective a-MSH processing as a fundamental mediator of enhanced GNG in the context of hypothalamic ER stress, and establish a-MSH deficiency in proopiomelanocortin (POMC) neurons as a potential contributor to the pathophysiology of T2D.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples