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Homo sapiens
27 Downloadable Samples
IlluminaHiSeq2500
Description
Compound Kushen Injection (CKI) has been clinically used in China for over 15 years to treat various types of solid tumours. However, because such Traditional Chinese Medicine (TCM) preparations are complex mixtures of plant secondary metabolites, it is essential to explore their underlying molecular mechanisms in a systematic fashion. We have used the MCF-7 breast cancer cell line as an initial in vitro model to identify CKI induced changes in gene expression. Cells were treated with CKI for 24 and 48 hours at two concentrations (1.0 and 2.0 mg/mL), and 5-Fluorouracil (5-FU) was used to treat cells as a positive control. Cell proliferation and apoptosis activity were measured with XTT and Caspase-3 assays respectively. Transcriptome data of cells treated with CKI or 5-FU for 24 and 48 hours were acquired using high-throughput Illumina RNA-seq technology. In this report we show that CKI inhibited MCF-7 cell proliferation and induced apoptosis in a dose-dependent fashion. We integrated and applied a series of transcriptome analysis methods, including gene differential expression analysis, pathway over-representation analysis, de novo identification of long non-coding RNAs (lncRNA) as well as co-expression network reconstruction, to identify candidate anti-cancer molecular mechanisms of CKI. Multiple pathways were perturbed and the cell cycle was identified as the potential primary target pathway of CKI in MCF-7 cells. CKI may also induce apoptosis in MCF-7 cells via a p53 independent mechanism. In addition, we identified novel lncRNAs and showed that many of them might be expressed as a response to CKI treatment. Overall, we have comprehensively investigated the utility of transcriptome analysis with high-throughput sequencing to characterise the molecular response of cancer cells to a TCM drug, and provided a practical guideline for future molecular studies of TCM. Overall design: High-depth paired-end RNA-seq from MCF-7 cell line. Each sample contains 3 biological replicates.
Publication Title
Identification of candidate anti-cancer molecular mechanisms of Compound Kushen Injection using functional genomics.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Numerous genetic variants associated with MEF2C are linked to autism, intellectual disability (ID) and schizophrenia (SCZ) – a heterogeneous collection of neurodevelopmental disorders with unclear pathophysiology. MEF2C is highly expressed in developing cortical excitatory neurons, but its role in their development remains unclear. We show here that conditional embryonic deletion of Mef2c in cortical and hippocampal excitatory neurons (Emx1-lineage) produces a dramatic reduction in cortical network activity in vivo, due in part to a dramatic increase in inhibitory and a decrease in excitatory synaptic transmission. In addition, we find that MEF2C regulates E/I synapse density predominantly as a cell-autonomous, transcriptional repressor. Analysis of differential gene expression in Mef2c mutant cortex identified a significant overlap with numerous synapse- and autism-linked genes, and the Mef2c mutant mice displayed numerous behaviors reminiscent of autism, ID and SCZ, suggesting that perturbing MEF2C function in neocortex can produce autistic- and ID-like behaviors in mice. Overall design: We carried out RNA-sequencing (RNA-seq) of somatosensory cortical tissue from control (Mef2cfl/fl) or Mef2c cKO (Mef2cfl/fl; Emx1-Cre) adult male mice. For the RNA-seq, three indipendent replicates were used for the mouse tissues.
Publication Title
MEF2C regulates cortical inhibitory and excitatory synapses and behaviors relevant to neurodevelopmental disorders.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 45 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Glucocorticoids (GC) are in most chemotherapy protocols for lymphoid malignancies, particularly childhood acute lymphoblastic leukaemia (ALL) for their ability to induce apoptosis in malignant blast. The underlying mechanism, however, has so far only been investigated in model systems. This study comprises Affymetrix hgu133 plus 2.0 analyses of
Publication Title
Identification of glucocorticoid-response genes in children with acute lymphoblastic leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Glucocorticoids (GC) are in most chemotherapy protocols for lymphoid malignancies, particularly childhood acute lymphoblastic leukaemia (ALL) for their ability to induce apoptosis in malignant blast. The underlying mechanism, however, has so far only been investigated in model systems. This study comprises Affymetrix hgu133 plus 2.0 analyses of
Publication Title
Identification of glucocorticoid-response genes in children with acute lymphoblastic leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples
GSE2843- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Glucocorticoids (GC) are in most chemotherapy protocols for lymphoid malignancies, particularly childhood acute lymphoblastic leukaemia (ALL) for their ability to induce apoptosis in malignant blast. The underlying mechanism, however, has so far only been investigated in model systems. This study comprises Affymetrix hgu133 plus 2.0 analyses of
Publication Title
Identification of glucocorticoid-response genes in children with acute lymphoblastic leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples GSE23591- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Primary mediastinal B-cell lymphoma (PMBL) and classical Hodgkin lymphoma (cHL) share a frequent constitutive activation of Janus-activated kinase (JAK) / signal transducer and activator of transcription (STAT) signaling pathway. Due to complex non-linear relations within the pathway, key dynamic properties remained to be identified to predict possible strategies for intervention. To untangle these features, we used dynamic pathway modeling that employs model development and calibration based on extensive quantitative data generation. Quantitative data were collected on JAK/STAT pathway signaling components in two lymphoma-derived cell lines, MedB-1 and L1236, representative of PMBL and cHL, respectively. We showed that the amounts of STAT5 and STAT6 are higher whereas the amount of SHP1 is lower in the two lymphoma cell lines compared to B cells from healthy donors. Distinctively, L1236 cells harbor more JAK2 and less SHP1 molecules per cell than MedB-1 or control cells. In our experimental setting interleukin-13 (IL13) stimulation levels remained constant over time. In MedB-1 cells surface IL13 receptor alpha 2 had a strong IL13-sequestering/decoy function. In both lymphoma cell lines we observed IL13-induced activation of interleukin-4 receptor alpha, JAK2 and STAT5, but not of STAT6, which was highly phosphorylated even without stimulus. Furthermore, the known STAT-inducible negative regulators CISH and SOCS3 were up-regulated within 2 hours in MedB-1 but not in L1236 cells. Global transcription profiling revealed 11 early and 16 sustained common genes up-regulated by IL13 in both lymphoma cell lines. Based on this detailed information we established two individual mathematical models, MedB-1 and L1236 model, which were able to describe the respective experimental data. Sensitivity analysis of the model identified six possible therapeutic targets able to reduce gene expression levels in L1236 cells and three in MedB-1 cells. By inhibition of STAT5 phosphorylation we successfully validated one of the predicted targets demonstrating the potential of the approach in guiding target identification for highly deregulated signaling networks in cancer cells. We established mathematical models of the JAK/STAT pathway in two lymphoma cell types (PMBL and cHL), able to reproduce experimental data and to predict possible therapeutic targets.
Publication Title
Dynamic mathematical modeling of IL13-induced signaling in Hodgkin and primary mediastinal B-cell lymphoma allows prediction of therapeutic targets.
Sample Metadata Fields
Cell line, Time
View Samples- Mus musculus
- 13 Downloadable Samples
- Illumina HiSeq 1500
Description
Recent reports have proposed a new paradigm for obtaining mature somatic cell types from fibroblasts without going through a pluripotent state, by briefly expressing canonical iPSC reprogramming factors Oct4, Sox2, Klf4 and c-Myc (abbreviated as OSKM), in cells expanded in lineage differentiation promoting conditions. Here we apply genetic lineage tracing for endogenous Nanog, Oct4 and X chromosome reactivation during OSKM induced trans-differentiation, as these molecular events mark final stages for acquisition of induced pluripotency. Remarkably, the vast majority of reprogrammed cardiomyocytes or neural stem cells derived from mouse fibroblasts via OSKM mediated trans-differentiation were attained after transient acquisition of pluripotency, and followed by rapid differentiation. Our findings underscore a molecular and functional coupling between inducing pluripotency and obtaining “trans-differentiated” somatic cells via OSKM induction, and have implications on defining molecular trajectories assumed during different cell reprogramming methods. Overall design: poly RNA-Seq was measured before, during and after conversion of mouse embryonic fibroblasts to neural stem cells using OSKM trans-differentiation method.
Publication Title
Transient acquisition of pluripotency during somatic cell transdifferentiation with iPSC reprogramming factors.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The H3K27 demethylase Utx regulates somatic and germ cell epigenetic reprogramming.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Pluripotency can be induced in somatic cells by ectopic expression of defined transcription factors, however the identity of epigenetic regulators driving the progression of cellular reprogramming requires further investigation. Here we uncover a non-redundant role for the JmjC-domain-containing protein histone H3 methylated Lys 27 (H3K27) demethylase Utx, as a critical regulator for the induction, but not for the maintenance, of primed and nave pluripotency in mice and in humans. Utx depletion results in aberrant H3K27me3 repressive chromatin demethylation dynamics, which subsequently hampers the reactivation of pluripotency promoting genes during reprogramming. Remarkably, Utx deficient primordial germ cells (PGCs) display a cell autonomous aberrant epigenetic reprogramming in vivo during their embryonic maturation, resulting in the lack of functional contribution to the germ-line lineage.
Publication Title
The H3K27 demethylase Utx regulates somatic and germ cell epigenetic reprogramming.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Rattus norvegicus
- 36 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Protein and mRNA levels for several selenoproteins, such as glutathione peroxidase-1 (Gpx1), are down-regulated dramatically by selenium (Se) deficiency.
Publication Title
Selenium toxicity but not deficient or super-nutritional selenium status vastly alters the transcriptome in rodents.
Sample Metadata Fields
Specimen part, Treatment
View Samples