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GSE47104
Mus musculus
4 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Skeletal muscle aging results in a gradual loss of skeletal muscle mass, skeletal muscle function and decreased regenerative capacity, which can lead to sarcopenia and increased mortality. While the mechanisms underlying sarcopenia remain unclear, the skeletal muscle stem cell, or satellite cell, is required for muscle regeneration. Therefore, identification of signaling pathways affecting satellite cell function during aging may provide insights into therapeutic targets for combating sarcopenia. Here, we show that a cell-autonomous loss in self-renewal occurs via novel alterations in FGF and p38 MAPK signaling in old satellite cells. We further demonstrate that pharmacological manipulation of these pathways can ameliorate age-associated self-renewal defects. Thus, our data highlight an age-associated deregulation of a satellite cell homeostatic network and reveals potential therapeutic opportunities for the treatment of progressive muscle wasting.
Publication Title
p38 MAPK signaling underlies a cell-autonomous loss of stem cell self-renewal in skeletal muscle of aged mice.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 7 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The seed maturation program occurs only during late phase of embryo development and repression of the maturation genes is pivotal for seedling development. However, mechanisms that repress the expression of this program in vegetative tissues are not well understood. A genetic screen was performed for mutants that express maturation genes in leaves. Here, it is shown that mutations affecting SDG8 (SET DOMAIN GROUP 8), a putative histone methyltransferase, cause ectopic expression of a subset of maturation genes in leaves. Further, to investigate the relationship between SDG8 and the Polycomb Group (PcG) proteins, which are known to repress many developmentally important genes including seed maturation genes, double mutants was made and formation of somatic embryos was observed on mutant seedlings with mutations in both SDG8 and EMF2 (EMBRYONIC FLOWER 2). Interestingly, double mutant of sdg8 and mutations in VRN2 (VERNALIZATION 2), a paralog of EMF2, grow and develop normally to maturity. Analysis of histone methylation status at chromatins of a number of maturation loci revealed synergistic effect of emf2 and sdg8 on the deposition of the active histone mark, trimethylation of lysine 4 on histone 3 (H3K4me3), which is consistent with high expression of these genes (formation of somatic embryos) in emf2 sdg8 double mutants. These observations demonstrate a functional cooperative interplay between SDG8 and an EMF2-containing PcG complex in maintaining vegetative cell identity by repressing seed genes to promote seedling development. The work also indicates the functional specificities of PcG complexes in Arabidopsis.
Publication Title
Synergistic repression of the embryonic programme by SET DOMAIN GROUP 8 and EMBRYONIC FLOWER 2 in Arabidopsis seedlings.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
In response to the cytokines, macrophage colony-stimulating factor and receptor activator of NF-kB ligand, monocyte precursors differentiate into bone marrow-derived macrophages (BMDMs) that ultimately fuse to form multi-nucleated osteoclasts, following a tightly controlled genetic program where specific sets of genes are differentially expressed.
Publication Title
Osteoclast-mediated bone resorption is controlled by a compensatory network of secreted and membrane-tethered metalloproteinases.
Sample Metadata Fields
Age, Specimen part, Time
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Synthesis and accumulation of seed storage proteins (SSPs) is an important aspect of the seed maturation program. Genes encoding SSPs are specifically and highly expressed in the seed during maturation. However, the mechanisms that repress the expression of these genes in leaf tissue are not well understood. To gain insight into the repression mechanisms, we have performed a transgenic screening for mutants that express SSPs in leaves. Here we show that mutations of BRAHMA (BRM), a SNF2 chromatin remodelling ATPase, cause the ectopic expression of a subset of SSPs and other embryogenesis related genes in leaf tissue. Consistent with the notion that such SNF2-like ATPases form protein complexes in vivo, we observed similar phenotypes for mutations of AtSWI3C, a BRM interacting partner, and BSH, a SNF5 homolog and essential SWI/SNF subunit. Further, we present chromatin immunoprecipitation evidence that BRM is recruited to the promoters of a number of embryogenesis genes including the 2S genes, which are expressed/elevated in brm leaves. Consistent with its role in nucleosome remodelling, BRM appears to control the chromatin structure of the At2S2 promoter. These results show that a BRM-containing chromatin remodelling ATPase complex is involved in the direct repression of SSPs in leaf tissue.
Publication Title
The Arabidopsis BRAHMA chromatin-remodeling ATPase is involved in repression of seed maturation genes in leaves.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
IlluminaHiSeq2000
Description
Anti-angiogenic therapy is commonly used for the treatment of CRC. Although patients derive some clinical benefit, treatment resistance inevitably occurs. The MET signaling pathway has been proposed to be a major contributor of resistance to anti-angiogenic therapy. MET is upregulated in response to VEGF pathway inhibition and plays an essential role in tumorigenesis and progression of tumors. In this study we set out to determine the efficacy of cabozantinib in a preclinical CRC PDTX model. We demonstrate potent inhibitory effects on tumor growth in 80% of tumors treated. The greatest antitumor effects were observed in tumors that possess a mutation in the PIK3CA gene. The underlying antitumor mechanisms of cabozantinib consisted of inhibition of angiogenesis and Akt activation and significantly decreased expression of genes involved in the PI3K pathway. These findings support further evaluation of cabozantinib in patients with CRC. PIK3CA mutation as a predictive biomarker of sensitivity is intriguing and warrants further elucidation. A clinical trial of cabozantinib in refractory metastatic CRC is being activated. Overall design: CRC PDTX Model treated with cabozantinib
Publication Title
Potent antitumor activity of cabozantinib, a c-MET and VEGFR2 inhibitor, in a colorectal cancer patient-derived tumor explant model.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Adaptive immune responses to infection result in the formation of memory T cells that respond more rapidly and robustly to reinfections, providing the basis of the immunological memory targeted by vaccines. Underlying the enhanced responsiveness of memory cells is their ability to rapidly up-regulate the transcription of key effector genes at a higher level compared to nave cells (termed transcriptional memory). While transcriptionally permissive histone modifications are known to provide chromatin structures that facilitate transcriptional memory, the molecular mechanisms that underpin this process still remain elusive. Here we investigate the transcriptional response of the Jurkat T cell line to stimulation with PMA and Ionomycin and determine if this response differs in cells that have seen stimuli previously.
Publication Title
Nuclear PKC-θ facilitates rapid transcriptional responses in human memory CD4+ T cells through p65 and H2B phosphorylation.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
AP2 transcription factors play important roles in development and cancer, we tried to clarify the role of the so far uncharacterised TFAP2E in colorectal cancer.
Publication Title
TFAP2E-DKK4 and chemoresistance in colorectal cancer.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 27 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Long noncoding RNAs regulate adipogenesis.
Sample Metadata Fields
Specimen part, Disease
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Adipogenesis involves the regulation of hundreds of genes by several well-studied proteins, but the role of long, noncoding RNAs in this process has not been defined. We track the regulation of hundreds of lncRNAs during adipocyte differentiation, and find several that are essential for this process.
Publication Title
Long noncoding RNAs regulate adipogenesis.
Sample Metadata Fields
Specimen part, Disease
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina Genome Analyzer
Description
Adipogenesis involves the regulation of hundreds of genes by several well-studied proteins, but the role of long, noncoding RNAs in this process has not been defined. We track the regulation of hundreds of lncRNAs during adipocyte differentiation, and find several that are essential for this process. Overall design: We extractedbrown and white primary adipocytes and pre-adipocytes and profiled lncRNA expresssion via mRNA-Seq. We also profiled cultured, differentiated adipocytes to verify that we could recapitulate the adipocyte expression profile in preparation for a loss-of-function screen for essential adipogenic lincRNAs.
Publication Title
Long noncoding RNAs regulate adipogenesis.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples