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SRP156461
Mus musculus
17 Downloadable Samples
Illumina HiSeq 2500
Description
We show that mesenchymal CSC-like cells express an embryonic stem cell signature that is mutant p53 dependent Overall design: Examination of three p53 mutant mesenchymal stem cells and ten derived CSC-like cell lines and 2 derived p53 mutant KO clones compared to control clones
Publication Title
A Mutant p53-Dependent Embryonic Stem Cell Gene Signature Is Associated with Augmented Tumorigenesis of Stem Cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Liver samples of mice harboring liver-specific deletion of Lats2 (Lats2-CKO) were compared to WT mice.
Publication Title
The LATS2 tumor suppressor inhibits SREBP and suppresses hepatic cholesterol accumulation.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 14 Downloadable Samples
- Illumina HiSeq 2500
Description
Deregulated activity of the LATS tumor suppressors has broad implications on cellular and tissue homeostasis. We examined the consequences of downregulation of either LATS1 or LATS2 in breast cancer. Consistent with their proposed tumor suppressive roles, expression of both paralogs is significantly downregulated in human breast cancer, and loss of either paralog accelerated mammary tumorigenesis in mice. However, each paralog had a distinct impact on breast cancer. Thus, LATS2 depletion in luminal B tumors resulted in metabolic rewiring, with increased glycolysis and reduced PPARg signaling. Furthermore, pharmacological activation of PPARg elicited LATS2-dependent death in luminal B-derived cells. In contrast, LATS1 depletion augmented cancer cell plasticity, skewing luminal B tumors towards increased expression of basal-like features, in association with increased resistance to hormone therapy. Hence, these two closely related paralogs play distinct roles in protection against breast cancer; tumors with reduced expression of either LATS1 or LATS2 may rewire signaling networks differently and thus respond differently to anti-cancer treatments. Overall design: RNA was isolated from Lats1-CKO and Lats2-CKO PyMT tumors (4 samples from each). For each genotype, the corresponding wt littermate controls were used (3 samples in each batch).
Publication Title
LATS1 and LATS2 suppress breast cancer progression by maintaining cell identity and metabolic state.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Human mononuclear cells were cultured in 2 phases. In the 1st phase the culture medium contained cyclosporine A the 2nd phase contained SCF and erythropoietin. Cells were collected at 3 stages of differentiation; on day 6, 10, 12 and represented early erythroblasts, medium stage and normoblasts.
Publication Title
Identification of gene networks associated with erythroid differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 19 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
We profiled the transcriptome of Drosophila melanogaster embryos in ttk2D50 embryos or after over-expression using btl-GAL4; UAS-ttk, respectively. We further isolated cells that express btl-enh-RFPmoe (Cabernard and Affolter 2005) and FACS sorting, and profiled their transcriptomes in the same genetic backgrounds.
Publication Title
Tramtrack is genetically upstream of genes controlling tracheal tube size in Drosophila.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 135 Downloadable Samples
- NextSeq 500
Description
Multiple myeloma (MM), a plasma cell (PC) malignancy, is the second most common blood cancer. Despite extensive research, disease heterogeneity within and between patients is poorly characterized, hampering efforts for early diagnosis and improved treatments. Here, we apply single cell RNA-seq to study the heterogeneity of 40 individuals along the MM progression spectrum. We define malignant PC at single cell resolution, demonstrating high inter-patient variability that can be explained by expression of known MM drivers and additional putative factors. Within newly diagnosed patients, we identify extensive sub-clonal structures for 10/29 patients. In asymptomatic patients with early disease and in minimal residual disease post-treatment, we detect tumor PC for a subset of the patients, with the same drivers of active myeloma. Single cell analysis of rare circulating tumor cells (CTC) allows detection of malignant PC, which reflect the BM disease. Our work establishes scRNA-seq for dissecting blood malignancies and devising detailed molecular characterization of tumor cells in symptomatic and asymptomatic patients. Overall design: The study includes 29 newly diagnosed patients with plasma cell neoplasms and 11 control donors, for which bone marrow plasma cells were single cell sorted by FACS, and their mRNA sequenced. For 11 patients, targeted genomic DNA panel analysis for myeloma was performed.
Publication Title
Single cell dissection of plasma cell heterogeneity in symptomatic and asymptomatic myeloma.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Safety sciences and the identification chemical hazard have been seen as one of the most immediate practical applications of human pluripotent stem cell technology. Protocols for the generation of many desirable human cell types have been developed, but optimization of neuronal models for toxicological use has been astonishingly slow, and the wide, clinically- important field of peripheral neurotoxicity is still largely unexplored. Here, a 2-step protocol to generate large lots of identical peripheral human neuronal precursors was characterized and adapted to the measurement of peripheral neurotoxicity. High content imaging allowed an unbiased assessment of cell morphology and viability. The computational quantification of neurite growth as functional parameter highly sensitive to disturbances by toxicants was used as endpoint reflecting specific neurotoxicity. The differentiation of cells towards dorsal root ganglia neurons was tracked in relation to a large background data set based on gene expression microarrays. On this basis, a peripheral neurotoxicity (PeriTox) test was developed as first toxicological assay that harnesses the potential of human pluripotent stem cells to generate cell types/tissues that are not otherwise available for prediction of human systemic organ toxicity. Testing of more than 30 chemicals showed that human neurotoxicants, as well as neurite growth enhancers, were correctly identified. Various classes of chemotherapeutics causing human peripheral neuropathies were identified, while they were missed when tested on human central neurons. The PeriTox-test established here shows the potential of human stem cells for clinically-relevant safety testing of drugs in use and of new emerging candidates.
Publication Title
Stem Cell-Derived Immature Human Dorsal Root Ganglia Neurons to Identify Peripheral Neurotoxicants.
Sample Metadata Fields
Sex, Specimen part, Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Monocyte chemoattractant protein 1 (MCP-1/CCL2) is critically involved in directing the migration of blood monocytes to sites of inflammation. Consequently, excessive MCP-1 secretion has been linked to many (auto)inflammatory diseases, whereas a lack of expression severely impairs immune responsiveness. We demonstrate that the atypical inhibitor of NF-B (IB), a transcriptional co-activator required for the selective expression of a subset of NF-B target genes, is a key activator of the Ccl2 gene. IB-deficient macrophages exhibited impaired secretion of MCP-1 when challenged with diverse inflammatory stimuli, such as lipopolysaccharide or peptidoglycan. These findings were reflected at the level of Ccl2 gene expression, which was tightly coupled to the presence of IB. Moreover, mechanistic insights acquired by chromatin immunoprecipitation demonstrate that IB is directly recruited to the proximal promoter region of the Ccl2 gene and required for histone H3K9 trimethylation. Finally, IB-deficient mice showed significantly impaired MCP-1 secretion and monocyte infiltration in an experimental model of peritonitis. Together, these findings suggest a distinguished role of IB in mediating the targeted recruitment of monocytes in response to local inflammatory events.
Publication Title
IκBζ is a transcriptional key regulator of CCL2/MCP-1.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 91 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Tofacitinib is an oral Janus kinase inhibitor being investigated for psoriasis. We sought to elucidate the molecular mechanisms underlying the clinical efficacy of tofacitinib in patients with psoriasis. Twelve patients with plaque psoriasis were randomized (3:1) to receive 10mg of tofacitinib or placebo twice daily for 12weeks. Biopsy specimens were taken from nonlesional (baseline) and lesional (baseline, days 1 and 3, and weeks 1, 2, 4, and 12) skin. Biopsy specimens were examined for psoriatic epidermal features (thickness, Ki67+ keratinocytes and keratin 16 [KRT16] mRNA expression, and phosphorylated signal transducer and activator of transcription [pSTAT]+ nuclei) and T-cell and dendritic cell (DC) subsets by using immunohistochemistry, and mRNA transcripts were quantified by using a microarray. In lesional skin keratinocyte pSTAT1 and pSTAT3 staining was increased at baseline but reduced after 1day of tofacitinib (baseline, median of 1290 pSTAT1+ cells/?m2; day 1, median of 332 pSTAT1+ cells/?m2; and nonlesional, median of 155 pSTAT1+ cells/?m2). Epidermal thickness and KRT16 mRNA expression were significantly and progressively reduced after days 1 and 3 of tofacitinib administration, respectively (eg, KRT16 decreased 2.74-fold, day 3 vs baseline, P=.016). Decreases in DC and T-cell numbers were observed after weeks 1 and 2, respectively. At week 4, significant decreases in IL-23/TH17 pathways were observed that persisted through week 12. Improvements in clinical and histologic features were strongly associated with changes in expression of psoriasis-related genes and reduction in IL-17 gene expression. Tofacitinib has a multitiered response in patients with psoriasis: (1) rapid attenuation of keratinocyte Janus kinase/STAT signaling; (2) removal of keratinocyte-induced cytokine signaling, leading to reductions in pathologic DC andT-cell numbers to nonlesional levels; and (3) inhibition of the IL-23/TH17 pathway.
Publication Title
Tofacitinib attenuates pathologic immune pathways in patients with psoriasis: A randomized phase 2 study.
Sample Metadata Fields
Specimen part, Disease, Treatment, Subject, Time
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The involvement of skeletal muscle in the process of palatal development in mammals is an example of Waddingtonian epigenetics. Our earlier study showed that the cleft palate develops in the complete absence of skeletal musculature during embryonic development in mice. This contrasts with previous beliefs that tongue obstruction prevents the elevation and fusion of the palatal shelves. We argue that the complete absence of mechanical stimuli from the adjacent muscle, i.e., the lack of both static and dynamic loading, results in disordered palatogenesis. We further suggest that proper fusion of the palatal shelves depends not only on mechanical but also on paracrine contributions from the muscle. The muscle's paracrine role in the process of palatal fusion is achieved through its being a source of certain secreted and/or circulatory proteins.
Publication Title
Role of skeletal muscle in palate development.
Sample Metadata Fields
Specimen part
View Samples