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SRP064115
Mus musculus
24 Downloadable Samples
Illumina HiSeq 2500
Description
Mediator is regarded a general co-activator of RNA-Polymerase II dependent transcription but not much is known about its function and regulation in mouse pluripotent embryonic stem cells (mESC). One means of controlling Mediator function is provided by binding of the Cdk8 module (Med12, Cdk8, Ccnc and Med13) to Mediator. Here we report that the Cdk8 module subunit Med12 operates together with PRC1 to silence developmental key genes in the pluripotent state. At the molecular level, PRC1 is required to assemble ncRNA containing Med12-Mediator complexes at promoters of repressed genes. In the course of cellular differentiation the H2A-ubiquitin binding protein Zrf1 abrogates PRC1-Med12 binding and facilitates the recruitment of Cdk8 into Mediator. Remodeling of the Mediator-associated protein complex converts Mediator into a transcriptional enhancer that mediates ncRNA-dependent activation of Polycomb target genes Overall design: RNAseq of pluripotent (control, shNMC, shRing1b, shMed12, shCdk8, shZrf1) and early differentiating (control, shNMC, shMed12, shCdk8, shZrf1) stem cells in triplicates. Control would be normal E14TG2A mESCs. shNMC refers to E14TG2A cells stably transfected with a short hairpin that has no mammalian targets (Non Mammalian Control). All the other samples are indeed stably transfected with short hairpins against the indicated genes.
Publication Title
Dual role of Med12 in PRC1-dependent gene repression and ncRNA-mediated transcriptional activation.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- NextSeq 500
Description
The bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-4 (PFKFB4) controls metabolic flux through allosteric regulation of glycolysis. Here we show that p53 regulates the expression of PFKFB4 and that p53-deficient cancer cells are highly dependent on the function of this enzyme. We found that p53 down-regulates PFKFB4 expression by binding to its promoter and mediating transcriptional repression via histone deacetylases. Depletion of PFKFB4 from p53 deficient cancer cells increased levels of the allosteric regulator fructose 2,6-bisphophate, leading to increased glycolytic activity but decreased routing of metabolites through the oxidative arm of the pentose phosphate pathway. PFKFB4 was also required to support the synthesis and regeneration of nicotinamide adenine dinucleotide phosphate (NADPH) in p53 deficient cancer cells. Moreover, depletion of PFKFB4 attenuated cellular biosynthetic activity and resulted in the accumulation of reactive oxygen species and cell death in the absence of p53. Finally, silencing of PFKFB4 induced apoptosis in p53 deficient cancer cells in vivo and interfered with tumour growth. These results demonstrate that PFKFB4 is essential to support anabolic metabolism in p53-deficient cancer cells and suggest that inhibition of PFKFB4 could be an effective strategy for cancer treatment. Overall design: Gene expression changes in HCT116 p53+/+ and p53-/- xenograft tumours after PFKFB4 silencing
Publication Title
6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 is essential for p53-null cancer cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 19 Downloadable Samples
- Illumina HiSeq 2500
Description
Early innate lymphoid progenitors (EILP) have recently been identified in the mouse adult bone marrow as a multipotential progenitor population committed to ILC lineages, but their relationship with other described ILC progenitors is still unclear. In this study, we examine the progenitor-successor relationships between EILP, IL-7R+ common lymphoid progenitors (ALP), and ILC precursors (ILCp). Bioinformatic, phenotypical, functional, and genetic approaches collectively establish EILP as an intermediate progenitor between ALP and ILCp. Our work additionally provides new candidate regulators of ILC development and clearly defines the stage of requirement of transcription factors key for early ILC development. Overall design: transcriptional profiling of early ILC progenitors (EILP, ILCp), and common lymphoid progenitors (ALP) was performed by RNA sequencing
Publication Title
Development and differentiation of early innate lymphoid progenitors.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Gene expression profiling was performed to identify INSL4-regulated gene program in non-small cell lung cancer A549 cells. We compared gene expression profiles of A549 cells transduced with lentiviruses expressing scrambled shRNA control or INSL4 shRNA. Our analysis revealed INSL4-regulated gene program that are involved in the regulation of cell cycle, growth and survival.
Publication Title
Role of INSL4 Signaling in Sustaining the Growth and Viability of LKB1-Inactivated Lung Cancer.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Gene expression profiling was performed on control and long intergenic non-protein coding RNA 473 (LINC00473)-depleted human mucoepidermoid carcinoma H3118 cells, and differentially expressed genes after LINC00473 depletion were identified.
Publication Title
CRTC1-MAML2 fusion-induced lncRNA LINC00473 expression maintains the growth and survival of human mucoepidermoid carcinoma cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 7 Downloadable Samples
- IlluminaHiSeq2000
Description
Neuronal migration defects (NMDs) are among the most common and severe brain abnormalities in humans. Lack of disease models in mice or in human cells has hampered the identification of underlying mechanisms. From patients with severe NMDs we generated iPSCs then differentiated neural progenitor cells (NPCs). On artificial extracellular matrix, patient-derived neuronal cells showed defective migration and impaired neurite outgrowth. From a cohort of 107 families with NMDs, sequencing identified two homozygous C-terminal truncating mutations in CTNNA2, encoding aN-catenin, one of three paralogues of the a-catenin family, involved in epithelial integrity and cell polarity. Patient-derived or CRISPR-targeted CTNNA2- mutant neuronal cells showed defective migration and neurite stability. Recombinant aN-catenin was sufficient to bundle purified actin and to suppress the actin-branching activity of ARP2/3. Small molecule inhibitors of ARP2/3 rescued the CTNNA2 neurite defect. Thus, disease modeling in human cells could be used to understand NMD pathogenesis and develop treatments for associated disorders. Overall design: 2 biological replicates per individual (2 iPSC clone differentiations), excluding 1263A, which has one sample
Publication Title
Biallelic loss of human CTNNA2, encoding αN-catenin, leads to ARP2/3 complex overactivity and disordered cortical neuronal migration.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
- NextSeq 500, Ion Torrent Proton
Description
ILC210 represent a distinct effector population of ILC2 cells that have regulatory potential Overall design: comparison between ILC2 cells with IL-33 stimulation or not on transcriptome change
Publication Title
Alternative activation generates IL-10 producing type 2 innate lymphoid cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Ion Torrent Proton
Description
Subtypes of innate lymphoid cells (ILC), defined by effector function and transcription factor expression, have recently been identified. In the adult, ILC derive from common lymphoid progenitors in bone marrow, although transcriptional regulation of the developmental pathways involved remains poorly defined. TOX is required for development of lymphoid tissue inducer cells, a type of ILC3 required for lymph node organogenesis, and NK cells, a type of ILC1. We show here that production of multiple ILC lineages requires TOX, as a result of TOX-dependent development of common ILC progenitors. Comparative transcriptome analysis demonstrated failure to induce various aspects of the ILC gene program in the absence of TOX, implicating this nuclear factor as a key early determinant of ILC lineage specification. Overall design: TOX KO vs. wild tyype
Publication Title
The development of innate lymphoid cells requires TOX-dependent generation of a common innate lymphoid cell progenitor.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 57 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Subcutaneous adipose tissue gene expression and DNA methylation respond to both short- and long-term weight loss.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Homo sapiens
- 57 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To understand the temporal changes occurring in adipose tissue gene expression during a one-year weightloss intervention, adipose tissue biopsies were collected from 19 healthy obese individuals at three time points.
Publication Title
Subcutaneous adipose tissue gene expression and DNA methylation respond to both short- and long-term weight loss.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples