The goal of this study is to define genes that are differentially expressed in Down syndrome leukemic blasts after treatment with valproic acid (VPA)
Histone deacetylase inhibitors induce apoptosis in myeloid leukemia by suppressing autophagy.
Specimen part, Treatment
View SamplesStandard chemotherapy is the only systemic treatment for triple-negative breast cancer (TNBC). Despite the good initial responses, resistance remains a major therapeutic obstacle. Here, we employed a High-Throughput Screen to identify targeted therapies that overcome chemoresistance in TNBC. We applied short-term paclitaxel treatment and screened 320 small-molecule inhibitors of known targets to identify drugs that preferentially and efficiently target paclitaxel-treated TNBC cells. Among these compounds the SMAC mimetics (BV6, Birinapant) and BH3-mimetics (ABT-737/263) were recognized as potent targeted therapy for multiple paclitaxel-residual TNBC cell lines. However, acquired paclitaxel resistance through repeated paclitaxel pulses result in desensitization to BV6, but not to ABT-263, suggesting that short- and long-term paclitaxel resistance are mediated by distinct mechanisms. Gene expression profiling of paclitaxel-residual, -resistant and nave MDA-MB-231 cells demonstrated that paclitaxel-residual, as opposed to -resistant cells, were characterized by an apoptotic signature, with downregulation of anti-apoptotic genes (BCL2, BIRC5), activation of apoptosis inducers (IL24, PDCD4), and enrichment of TNF/NF-B pathway, including upregulation of TNFSF15, coupled with cell-cycle arrest. BIRC5 and FOXM1 downregulation and IL24 induction was also evident in breast cancer patient datasets following taxane treatment. Exposure of nave and paclitaxel-resistant cells to supernatants of paclitaxel-residual cells sensitized them to BV6, and treatment with TNF enhanced the potency of BV6, suggesting that sensitization to BV6 is mediated, at least partially, by secreted factor(s). Our results suggest that administration of SMAC or BH3 mimetics following short-term paclitaxel treatment could be an effective therapeutic strategy for TNBC, while only BH3-mimetics could effectively overcome long-term paclitaxel resistance
Targeting of apoptotic pathways by SMAC or BH3 mimetics distinctly sensitizes paclitaxel-resistant triple negative breast cancer cells.
Sex, Age, Specimen part, Cell line, Treatment
View SamplesThese Affymetrix data were used to determine the role of each non-essential subunit of the conserved Ccr4-Not complex in the control of gene expression in the yeast S. cerevisiae. The study was performed with cells growing exponentially in high glucose and with cells grown to glucose depletion. Specific patterns of gene de-regulation were observed upon deletion of any given subunit, revealing the specificity of each subunits function. Consistently, the purification of the Ccr4-Not complex through Caf40p by tandem affinity purification from wild-type cells or cells lacking individual subunits of the Ccr4-Not complex revealed that each subunit had a particular impact on complex integrity. Furthermore, the micro-arrays revealed that the role of each subunit was specific to the growth conditions. From the study of only two different growth conditions, revealing an impact of the Ccr4-Not complex on more than 85% of all studied genes, we can infer that the Ccr4-Not complex is important for expression of most of the yeast genome.
Specific roles for the Ccr4-Not complex subunits in expression of the genome.
No sample metadata fields
View SamplesES cell lines were established from mouse embryos, which were homozygous for the Trim33-flox allele and carried the UbcCreERT2 transgene. Cells were cultured without feeder cells in the presence of LIF and 2i. Embryoid bodies (EBs) were generated using the ATCC protocol on low attachment dishes under differentiating conditions. EBs were induced with Tamoxifen at day 1 and harvested at days 2 and 2.5, respectively. Overall design: Investigate differentially expressed genes in control and Trim33-deficient embryoid bodies derived from mouse embryonic stem cells
Trim33 regulates early maturation of mouse embryoid bodies in vitro.
Specimen part, Cell line, Subject, Time
View SamplesWe used Arabidopsis full-genome microarrays to characterize plant transcript accumulations at different stages of infection with the biotrophic oomycete downy mildew pathogen, Hyaloperonospora arabidopsidis : initiation (< 1 dpi) and maintenance of infection (> 4 dpi).
An Arabidopsis (malectin-like) leucine-rich repeat receptor-like kinase contributes to downy mildew disease.
Specimen part
View SamplesWe have developed efficient protocols for the derivation of mesenchymal precursors from hESCs. While previous protocols were based on mesodermal induction via co-culture of hESCs on OP9 mouse stroma (Barberi et al., PLoS Biology, 2005), our recent work shows the derivation of hESC derived mesenchymal precurors under feeder-free conditions. The data presented here show a large and highly signficant overlap in global gene expression profiles between hESC derived mesenchymal precursors derived under feeder-free conditions with those derived via OP9 co-culure and mesenchymal precurosrs isolated directly from the adult bone marrow.
Derivation of engraftable skeletal myoblasts from human embryonic stem cells.
No sample metadata fields
View SamplesNotch signaling is widely implicated in mouse mammary gland development and tumorigenesis. To investigate the effects of acute activation of Notch signaling in the mammary epithelial compartment, we generated bi-transgenic MMTV-rtTA; TetO-NICD1 (MTB/TICNX) mice that conditionally express a constitutively active NOTCH1 intracellular domain (NICD1) construct in the mammary epithelium upon doxycycline administration.
Notch promotes recurrence of dormant tumor cells following HER2/neu-targeted therapy.
Sex, Age, Specimen part, Treatment, Time
View SamplesES cell lines were established from mouse embryos, which were homozygous for the Trim33-flox allele and carried the UbcCreERT2 transgene. Cells were cultured without feeder cells in the presence of LIF and 2i. Embryoid bodies (EBs) were generated using the ATCC protocol on low attachment dishes under differentiating conditions. EBs were induced with Tamoxifen at day 4 and harvested at day 7. Overall design: Investigate differentially expressed genes in control and Trim33-deficient embryoid bodies derived from mouse embryonic stem cells
Trim33 is required for appropriate development of pre-cardiogenic mesoderm.
Specimen part, Cell line, Subject, Time
View SamplesToxoplasma gondii is an obligate intracellular Apicomplexan parasite capable of invading and surviving within nucleated cells in most warm-blooded animals. This remarkable task is achieved through the delivery of effector proteins from the parasite into the parasitophorous vacuole and host cell cytosol that rewire host cellular pathways, facilitating parasite evasion of the immune system. Here, we have identified a novel export pathway in Toxoplasma that involves cleavage of effector proteins by the Golgi-resident aspartyl protease 5 (ASP5) prior to translocation into the host cell. We demonstrate that ASP5 cleaves a highly constrained amino acid motif that has some similarity to the PEXEL motif of Plasmodium parasites. We show that ASP5 can mature effectors at both the N- and C-terminal ends of proteins and is also required for the trafficking of proteins without this motif. Furthermore, we show that ASP5 controls establishment of the nanotubular network and is required for the efficient recruitment of host mitochondria to the parasitophorous vacuole membrane. Global assessment of host gene expression following infection reveals that ASP5-dependent pathways influence thousands of the transcriptional changes that Toxoplasma imparts on its host cell. This work characterizes the first identified machinery required for export of Toxoplasma effectors into the infected host cell. Overall design: Three groups of human foreskin fibroblasts are compared. Each group has 3 replicates giving a total of 9 samples. The first group of samples are infected with wild type (GRA16HA) Toxoplasma gondii, the second group with Asp5 knock-out Toxoplasma gondii, and the final group remain uninfected. All fibroblasts are generated from one donor sample.
An aspartyl protease defines a novel pathway for export of Toxoplasma proteins into the host cell.
No sample metadata fields
View SamplesFSHD and control immortalised myoblasts show repression of Pax7 target genes Overall design: FSHD Myoblasts 54-2, 54-12, 54-A5, 16A and 12A and matched controls 54-6, 54-A10, 16U and 12U were plated at 312,000 cells per 12 well plate in proliferation media and cultured for 48 hours or until 100% confluent. RNA-sequencing was performed on high quality (RIN > 8.0) DNA free RNA.
PAX7 target genes are globally repressed in facioscapulohumeral muscular dystrophy skeletal muscle.
Sex, Subject
View Samples