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GSE55587
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The tumor microenvironment plays a critical role in cancer progression, but the precise mechanisms by which stromal cells influence the tumor epithelium are poorly understood. The signaling adapter p62 has been implicated as a positive regulator of epithelial tumorigenesis; however, its role in the stroma is unknown. We show here that p62 levels are reduced in the stroma of several tumors. Also, orthotopic and organotypic studies demonstrate that the loss of p62 in the tumor microenvironment or stromal fibroblasts resulted in increased tumorigenesis of epithelial prostate cancer cells. The mechanism involves the regulation of cellular redox through an mTORC1/c-Myc pathway of stromal glucose and amino acid metabolism. Inhibition of the pathway by p62 deficiency results in increased stromal IL-6 production, which is required for tumor promotion in the epithelial compartment. Thus, p62 is an anti-inflammatory tumor suppressor that acts through modulation of metabolism in the tumor stroma.
Publication Title
Metabolic reprogramming of stromal fibroblasts through p62-mTORC1 signaling promotes inflammation and tumorigenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
Illumina HiSeq 2500
Description
One of the most common genetic alterations in acute myeloid leukemia is the internal tandem duplication (ITD) in the FLT3 receptor for cytokine FLT3 ligand (FLT3L). The constitutively active FLT3-ITD promotes the expansion of transformed progenitors, but also has pleiotropic effects on normal hematopoiesis. We analyzed the effect of FLT3-ITD on dendritic cells (DCs), which express FLT3 and can be expanded by FLT3L administration. We report that young pre-leukemic mice with the Flt3ITD knock-in allele manifest an expansion of all DCs including classical (cDCs) and plasmacytoid (pDCs). The expansion originated in DC progenitors, occurred in a cell-intrinsic manner and was further enhanced in Flt3ITD/ITD mice. The mutation caused the downregulation of Flt3 on the surface of DCs and reduced their responsiveness to Flt3L. Flt3ITD mice showed enhanced capacity to support T cell proliferation, including a cell-extrinsic expansion of regulatory T cells (Tregs). Accordingly, these mice restricted alloreactive T cell responses during graft-versus-host reaction, but failed to control autoimmunity in the absence of Tregs. Thus, the FLT3-ITD mutation directly affects DC development, thereby indirectly modulating T cell homeostasis and supporting Treg expansion. This effect of FLT3-ITD may subvert immunosurveillance and promote leukemogenesis in a cell-extrinsic manner. Overall design: Sorted splenic dendritic cell subsets from either Flt3+/+ or Flt3ITD/+ mice were sequenced for mRNA profiling. For each subset per genotype contains 2-3 replicates, all from independent experiments.
Publication Title
Leukemia-associated activating mutation of Flt3 expands dendritic cells and alters T cell responses.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Although bodyguard (bdg), lacerata (lcr) and fiddlehead (fdh) mutations affect three unrelated genes, they trigger similar effects, i.e. ectopic organ fusion, increase of cuticle permeability. After performing cutin and wax analyses on these Arabidopsis thaliana mutants, which did not coincide with the putative enzyme functions, we hypothesised that these mutations trigger a complex response which may be visible at the transcriptional level.
Publication Title
Dissection of the complex phenotype in cuticular mutants of Arabidopsis reveals a role of SERRATE as a mediator.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina HumanWG-6_V2_0_R2
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Promoter DNA methylation patterns of differentiated cells are largely programmed at the progenitor stage.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Ibf1 and Ibf2 are novel CP190-interacting proteins required for insulator function.
Sample Metadata Fields
Disease, Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip, Illumina HumanWG-6 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Epigenetic priming of inflammatory response genes by high glucose in adipose progenitor cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina HumanWG-6_V2_0_R2
Description
We surveyed DNA methylation profiles of all human RefSeq promoters in relation to gene expression and differentiation in adipose tissue, bone marrow and muscle mesenchymal progenitors, as well as in bone marrow-derived hematopoietic progenitors. We unravel strongly overlapping DNA methylation profiles between adipose stem cells (ASCs), bone marrow mesenchymal stem cells (BMMSCs) and muscle progenitor cells (MPCs), while hematopoietic progenitor cells (HPCs) are more epigenetically distant from MSCs seen as a whole. Differentiation resolves a fraction of methylation patterns common to MSCs, generating epigenetic divergence.
Publication Title
Promoter DNA methylation patterns of differentiated cells are largely programmed at the progenitor stage.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
The object of this study was to investigate the effect of elevated glucose concentrations (15 and 25 mM glucose) on gene expression in undifferentiated and adipogenic differentiated ASCs.
Publication Title
Epigenetic priming of inflammatory response genes by high glucose in adipose progenitor cells.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Gene expression in S2 cells after CG9740 or CP190 RNAi
Publication Title
Ibf1 and Ibf2 are novel CP190-interacting proteins required for insulator function.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
The aim of this study was to characterize basal gene expression for proliferating adipose tissue MSCs, cultured at normal cell culture conditions.
Publication Title
Epigenetic priming of inflammatory response genes by high glucose in adipose progenitor cells.
Sample Metadata Fields
Specimen part
View Samples