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SRP152507
Mus musculus
293 Downloadable Samples
Illumina HiSeq 2500
Description
Hematopoietic stem cells (HSCs) balance self-renewal and differentiation to maintain homeostasis. With aging, the frequency of polar HSCs decreases. Cell polarity in HSCs is controlled by the activity of the small RhoGTPase Cdc42. Here we demonstrate, using a comprehensive set of paired daughter cell analyses that include single cell 3D-confocal imaging, single cell transplants, single cell RNA-seq as well as single cell ATAC-seq, that the outcome of HSC divisions is strongly linked to the polarity status before mitosis, which is in turn determined by the level of the activity Cdc42 in stem cells. Aged apolar HSCs undergo preferentially self-renewing symmetric divisions, resulting in daughter stem cells with reduced regenerative capacity and lymphoid potential, while young polar HSCs undergo preferentially asymmetric divisions. Mathematical modeling in combination with experimental data implies a mechanistic role of the asymmetric sorting of Cdc42 in determining the potential of daughter cells via epigenetic mechanisms. Therefore, molecules that control HSC polarity might serve as modulators of the mode of stem cell division regulating the potential of daughter cells. Overall design: Sorted single cells were cultured with and without treatment in the presence of cytokines until first cell division (40-44hrs). The daughter cells were manually separated, washed with PBS and collected for RNA sequencing.
Publication Title
Aging alters the epigenetic asymmetry of HSC division.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 15 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
NRASG12V oncogene facilitates self-renewal in a murine model of acute myelogenous leukemia.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 32 Downloadable Samples
- Illumina HiSeq 2000
Description
Mutant RAS oncoproteins activate signaling molecules that drive oncogenesis in multiple human tumors including acute myelogenous leukemia (AML). However, the specific function of these pathways in AML is unclear. To elucidate the downstream functions of activated NRAS in AML, we employed a murine model of AML harboring Mll-AF9 and NRASG12V. We found that NRASG12V enforced leukemia self-renewal gene expression signatures and was required to maintain an MLL-AF9 and MYB-dependent gene expression program. In a multiplexed analysis of RAS-dependent signaling intermediates, the leukemia stem cell compartment was preferentially sensitive to RAS withdrawal. Use of RAS-pathway inhibitors showed that NRASG12V maintained leukemia self-renewal through mTOR and MEK pathway activation, implicating these pathways as potential targets for cancer stem cell-specific therapies. Overall design: Primary leukemia cells harvested from spleens were sorted into immunophenotypic subpopulations (Mac-1High, Mac-1LowKit–Sca-1–, Mac-1LowKit+Sca-1–, and Mac-1LowKit+Sca-1+). RNA was extracted from this subpopulations of cells and submitted for RNA sequencing.
Publication Title
NRASG12V oncogene facilitates self-renewal in a murine model of acute myelogenous leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Mutant RAS oncoproteins activate signaling molecules that drive oncogenesis in multiple human tumors including acute myelogenous leukemia (AML). However, the specific function of these pathways in AML is unclear. To elucidate the downstream functions of activated NRAS in AML, we employed a murine model of AML harboring Mll-AF9 and NRASG12V. We found that NRASG12V enforced leukemia self-renewal gene expression signatures and was required to maintain an MLL-AF9 and MYB-dependent gene expression program. In a multiplexed analysis of RAS-dependent signaling intermediates, the leukemia stem cell compartment was preferentially sensitive to RAS withdrawal. Use of RAS-pathway inhibitors showed that NRASG12V maintained leukemia self-renewal through mTOR and MEK pathway activation, implicating these pathways as potential targets for cancer stem cell-specific therapies.
Publication Title
NRASG12V oncogene facilitates self-renewal in a murine model of acute myelogenous leukemia.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Cell-type-specific control of enhancer activity by H3K9 trimethylation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Role of cell-type specific nucleosome positioning in inducible activation of mammalian promoters.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 13 Downloadable Samples
- IlluminaHiSeq2500
Description
The goal of this study is to compare the transcriptome of the 2 MVT1 subpopulations in order to identify new genes and pathways that stands beyond the CD24+ aggressive phenotype Overall design: mRNA profiles of CD24- and CD24+ cells were generated by deep sequencing, in triplicate, using Illumina HiSeq 2500
Publication Title
Deep sequencing of mRNA in CD24(-) and CD24(+) mammary carcinoma Mvt1 cell line.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
In dendritic cells, expression of the H3K9me3 demethylase JmjD2d is upregulated by LPS stimulation. To identify genes whose induction by LPS depends on JmjD2d activity, we performed a microarray analysis of wild-type and JmjD2d-knockdown dendritic cells, before and after stimulation with LPS.
Publication Title
Cell-type-specific control of enhancer activity by H3K9 trimethylation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We used microarrays to asses gene expression in 3T3 fibroblasts, after knock-down of Brg1 and Brm using stable shRNA interference. Cells were treated with 5ng/ml mouse TNF-alpha to stimulate inducible gene activation.
Publication Title
Role of cell-type specific nucleosome positioning in inducible activation of mammalian promoters.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Diet-induced obesity is characterized by macrophage (MF) infiltration and low-grade chronic inflammation in white adipose tissue (WAT) leading to insulin resistance. WAT MF are highly heterogeneous in their origin, patterns of gene expression and activities: unlike infiltrating monocyte-derived MF that promote inflammation and metabolic dysfunction, tissue-resident WAT MF originally described as ‘M2’ are phenotypically anti-inflammatory and counteract obesity and insulin resistance. Despite the critical role of the balance between these MF populations in metabolic homeostasis, the molecular mechanisms and key players that establish the resident MF transcription program are poorly understood. We recently reported that glucocorticoid receptor (GR)-interacting protein (GRIP)1 - a nuclear receptor coactivator - cooperates with GR to repress transcription of inflammatory genes. Here, using mice conditionally lacking GRIP1 in MF (cKO), we show that GRIP1 promotes MF polarization in response to IL4 (M2(IL4)) via a nuclear receptor-independent pathway by serving as a coactivator for Kruppel-like factor (KLF)4 – a critical driver of tissue MF differentiation. Interestingly, in vivo, GRIP1 cKO mice challenged with high-fat diet develop massive MF infiltration and chronic inflammation in WAT and liver, fatty livers, hyperglycemia, hyperinsulinemia and glucose intolerance consistent with metabolic syndrome phenotype. Together, our findings identify GRIP1 as a critical regulator of immunometabolism, which relies on distinct transcriptional mechanisms to coordinate the balance between MF populations in vivo thereby protecting mice from obesity-induced metabolic disease. Overall design: 1. Examination of IL4 induced transcriptome in in vitro differentiated primary bone marrow-derived macrophages. 2. Examination of macrophage transcriptome in macrophages isolated from the white adipose tissue of the WT and GRIP1(cKO) conditional KO animals
Publication Title
The transcriptional coregulator GRIP1 controls macrophage polarization and metabolic homeostasis.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples