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Mus musculus
16 Downloadable Samples
Illumina HiSeq 2000
Description
We show that key regulators of oxidative metabolism, the Estrogen Related Receptors (ERRs) and the PGC-1 co-activators, are transiently induced during somatic cell reprogramming. Bioenergetic assays reveal that while glycolysis increases throughout the reprogramming transition, the early stages feature a transient oxidative phosphorylation (OXPHOS) burst. Up-regulation of ERRa or ? is a prerequisite for the OXPHOS burst in human and mouse cells, respectively, and failure to induce this metabolic switch collapses the reprogramming process. We identify a Sca1-/CD34- sub-population of early reprogramming cells with enhanced ERR? and PGC-1ß expression as bona fide reprogramming progenitors. Transcriptional profiling confirmed that these progenitors have undergone extensive metabolic reprogramming. These studies characterize a previously unrecognized, ERR-dependent metabolic switch prior to establishment of induced pluripotency.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaHiSeq2500
Description
Human pancreatic adenocarcinoma cell line
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
- Illumina HiSeq 2500, Illumina HiSeq 2000
Description
We show that fat-resident regulatory T cells, termed fTregs, drive age-associated insulin resistance and can be specifically depleted to increase adipose insulin sensitivity. Comparative AdipoImmune profiling in young, aged, and obese mice reveals that fTregs progressively enrich in adipose as a function of age, but not obesity. fTreg-deficient mice are protected from age-associated insulin resistance and its accompanying physiological hallmarks. In contrast, fTreg-deficiency offers no protection from obesity-associated insulin resistance.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- IlluminaHiSeq2500
Description
To investigate the paracrine effects of stromal elements on cancer cells, we developed a “stromal” culture system, which incorporates structural and diffusible stroma-derived elements into homotypic cultures amenable to functional genomics and metabolomics. Here we show that microenvironmental cues co-regulate cancer metabolism and gene expression. Stromal inputs broadly influenced histone acetylation in the cancer epigenome, which coincided with induction of genes implicated in anabolic metabolism and inflammation. The gene expression and metabolic changes induced by stromal factors overlap with those previously identified following oncogenic Kras, suggesting functional complementarity between cell-autonomous and microenvironmental pathways. Finally, we implicate the BET family of epigenetic readers as key transducers of stromal inputs to drive alterations in gene expression. This work suggests paracrine epigenome regulation as a conduit through which stromal signals drive metabolic and immune adaptation to a challenging tumor microenvironment.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2000, Illumina HiSeq 2500
Description
We report that Rev-erba is targeted for ubiquitination and subsequent degradation by the F-box protein Fbxw7a, and identify the cyclin-dependent kinase 1 (Cdk1)-mediated phosphorylation of threonine 275 as necessary for the recruitment of the Fbxw7-dependent E3 ligase complex. In vitro, inhibition of Cdk1 kinase activity or mutation of T275 is sufficient to disrupt the Fbxw7-mediated Rev-erba degradation pathway. Moreover, genetic disruption of Fbxw7 in mouse liver dramatically alters the circadian expression of core clock genes and perturbs whole body lipid and glucose levels. These results reveal an additional level of regulation required for maintaining circadian rhythmicity, and reveal the essential roles of post-translational modifications in the coordination of the circadian clocks and metabolism through regulation of nuclear receptor protein stability.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 5 Downloadable Samples
- Illumina HiSeq 2000
Description
Estrogen-related receptor ? (ERR?) signaling increases during the neonatal to adult transition in pancreatic islet ß-cells. We show that ß-cell-specific ERR?-deficient (ßERR?KO) mice exhibit glucose intolerance with reduced glucose-stimulated insulin secretion (GSIS) and ßERR?KO islets have defective GSIS function accompanied by changes in genes that regulate ATP biosynthesis, oxidative phosphorylation, and the electron transport chain. ERR? overexpression enhances genes involved in mitochondrial metabolism, resulting in transformation of ß-like-cells into metabolically functional ß-cells that can ameliorate STZ-induced hyperglycemia in NOD-SCID mice. These results suggest that ERR? signaling is essential for the metabolic maturation of ß-like-cells and thus represents a novel therapeutic target in the treatment of diabetes.
Publication Title
ERRγ Is Required for the Metabolic Maturation of Therapeutically Functional Glucose-Responsive β Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
To investigate the paracrine effects of stromal elements on cancer cells, we developed a “stromal” culture system, which incorporates structural and diffusible stroma-derived elements into homotypic cultures amenable to functional genomics and metabolomics. Here we show that microenvironmental cues co-regulate cancer metabolism and gene expression. Stromal inputs broadly influenced histone acetylation in the cancer epigenome, which coincided with induction of genes implicated in anabolic metabolism and inflammation. The gene expression and metabolic changes induced by stromal factors overlap with those previously identified following oncogenic Kras, suggesting functional complementarity between cell-autonomous and microenvironmental pathways. Finally, we implicate the BET family of epigenetic readers as key transducers of stromal inputs to drive alterations in gene expression. This work suggests paracrine epigenome regulation as a conduit through which stromal signals drive metabolic and immune adaptation to a challenging tumor microenvironment.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples
SRP092624- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
Positive and negative selection processes in the thymus are critical steps for T cell maturation and self-tolerance. We show that decreased positive selection and excessive negative selection are attributable to T cell-specific nuclear receptor co-repressor 1 (NCoR1) deficiency. NCoR1 protects thymocytes from negative selection through the transcriptional repression of Bim expression. NCoR1 is also required for effective T cell response against microbial infection. Thus, NCoR1 sets the transcriptional threshold for coordinated positive selection and negative selection as well as optimal T cell immunity in periphery.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Age, Specimen part, Cell line
View Samples- Homo sapiens
- 3 Downloadable Samples
- IlluminaHiSeq2500
Description
We show that ERR? overexpression in ß-like-cells differentiated from human iPSCs enhances genes involved in mitochondrial metabolism, resulting in transformation of these cells into metabolically functional ß-cells that can ameliorate STZ-induced hyperglycemia in NOD-SCID mice. These results suggest that ERR? signaling is essential for the metabolic maturation of ß-like-cells and thus represents a novel therapeutic target in the treatment of diabetes.
Publication Title
ERRγ Is Required for the Metabolic Maturation of Therapeutically Functional Glucose-Responsive β Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 8 Downloadable Samples
Affymetrix Drosophila Genome Array (drosgenome1)
Description
THO2 and HPR1 proteins were co-depleted from Drosophila S2 cells and their role in mRNA export analysed by comparing total RNA and cytoplasmic RNA
Publication Title
The superhelical TPR-repeat domain of O-linked GlcNAc transferase exhibits structural similarities to importin alpha.
Sample Metadata Fields
Cell line
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