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SRP077462
Mus musculus
4 Downloadable Samples
Illumina HiSeq 2500
Description
Ets1-/- mice have an increase in B cell differentiation to plasma cells and increased serum immunoglobulin levels. The genes in B cells that are transcriptionally regulated by Ets1 and help regulate B cell differentiation are largely unknown. Here, we identify Ets1-regulated target genes in B cells using ChIP-seq and RNA-seq analysis. We found that Ets1 targets genes associated with immune response, mature B cell differentiation and regulation of B cell activation. Overall design: Quiescent follicular B cells were sorted from the spleens of wild-type and Ets1-/- mice using the following markers B220+ CD23-high CD21-low CD80-negative IgA-negative IgE-negative IgG1-negative IgG2a-negative IgG2b-negative IgG3-negative. Total RNA was prepared from sorted cells and subjected to RNA-sequencing.
Publication Title
Genome-Wide Identification of Target Genes for the Key B Cell Transcription Factor <i>Ets1</i>.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Gene expression analysis on purified murine hematopoietic stem cells (HSCs) deficient for Special AT-rich sequence-binding protein 1 (Satb1) compared to wild-type HSCs.
Publication Title
Satb1 regulates the self-renewal of hematopoietic stem cells by promoting quiescence and repressing differentiation commitment.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 19 Downloadable Samples
- Illumina HiSeq 2000
Description
Genomic studies in acute myeloid leukemias (AML) have identified mutations which drive altered DNA methylation, including TET2 and IDH. Functional studies have shown these mutations contribute to transformation, although how these mutations impact the response to epigenetic therapies is not fully delineated. Here we show AMLs with TET2/IDH2 mutations combined with FLT3ITD mutations are specifically sensitive to 5-Azacytidine or to the IDH2 inhibitor AG-221, respectively. 5-Azacytidine/AG-221 therapies induced a reduction in leukemic blasts and in stem/progenitor expansion, with attenuation of aberrant DNA hypermethylation. These therapeutic benefits were achieved through restoration of differentiation, such that normalized hematopoiesis was derived from mutant cells. Consistent with these data, at the time of clinical response to 5-Azacytidine or AG-221, most patients had mutant-derived hematopoiesis. By contrast, combined AG-221/5-Azacytidine plus FLT3 inhibition reduced disease burden and reversed epigenetic dysfunction. Our studies suggest combined targeting of signaling and epigenetic pathways can increase therapeutic response in AML. Overall design: We profiled genome-wide transcription patterns of the hematopoietic stem cells (LSK) population in Wild-type, Idh2 R140Q Flt3-ITD, and Tet2-/-;Flt3-IDT mice. Idh2 R140Q Flt3-ITD mice with AML were treated with either vehicle or AG-221 (the first small molecule in vivo inhibitor of IDH2 to enter clinical trials). Tet2-/-;Flt3-IDT mice with AML were treated with vehicle or 5-Azacytidine (Decitabine, hypomethylating agent).
Publication Title
Combination Targeted Therapy to Disrupt Aberrant Oncogenic Signaling and Reverse Epigenetic Dysfunction in <i>IDH2</i>- and <i>TET2</i>-Mutant Acute Myeloid Leukemia.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
- Illumina HiSeq 2500
Description
DNMT3A mutations are observed in myeloid malignancies, including myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS), and acute myeloid leukemia (AML). Here we investigated the impact of conditional hematopoietic Dnmt3a loss on disease phenotype in primary mice. Dnmt3a ablation led to a lethal, fully penetrant myeloproliferative neoplasm with myelodysplasia (MDS/MPN) characterized by marked, progressive hepatomegaly that was transplantable. We detected expanded stem/progenitor populations in the liver of Dnmt3a-ablated mice. Homing studies showed that Dnmt3a-deleted bone marrow cells preferentially migrated to the liver. Hence, in addition to the established role of Dnmt3a in regulating self-renewal, Dnmt3a regulates tissue tropism and limits myeloid progenitor expansion in vivo. Overall design: Dnmt3af/f mice (Nguyen et al) were crossed into hematopoietic-specific inducible Mx1-Cre deletor line; we examined transcriptomes from FACS-sorted LSK and GMP populations from Dnmt3af/f Mx1-Cre+ (KO) and Dnmt3af/f Mx1-Cre- (CTRL) animals at 12 months of age
Publication Title
Dnmt3a regulates myeloproliferation and liver-specific expansion of hematopoietic stem and progenitor cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Bos taurus
- 12 Downloadable Samples
- Bovine Gene 1.0 ST Array (bovgene10st)
Description
Reproductive success depends on a functional oviduct for gamete storage, maturation, fertilization, and early embryonic development. The ovarian-derived sex steroids estrogen and progesterone have been found to influence cell proliferation, differentiation and functionality of the oviduct. The objective of this study was to investigate steroidal regulation of oviductal epithelial cell function by using the Bovine Gene 1.0 ST array (Affymetrix Inc., CA) for transcriptional profiling. Our overall goals were to increase our understanding of known epithelial cell processes critical for fertility, and to identify novel genes and biochemical processes for future analysis. Transcripts were annotated using NetAffx annotation database for the Bovine gene 1.0 ST array and last updated in June 2014.
Publication Title
A transcriptomal analysis of bovine oviductal epithelial cells collected during the follicular phase versus the luteal phase of the estrous cycle.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 8 Downloadable Samples
- Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
In the present study, we sought to understand the impact of obesity/metabolic disease (high-fat induced) on spinal cord injury (SCI) by examining transcriptome. Adult, male Long Evans rats received either thoracic level contusion of the spinal cord or sham laminectomy and then were allowed to recover on normal rat chow for 4 weeks and further on HFD for an additional 8 weeks. Spinal cord tissues harvested from the rats were processed for Affymetrix microarray and further transcriptomic analysis.
Publication Title
Chronic spinal cord changes in a high-fat diet-fed male rat model of thoracic spinal contusion.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
microRNA-126 is a microRNA predominately expressed by endothelial cells and controls angiogenesis. Unexpectedly, we found that mice deficient in miR-126 have a major impairment in their innate response to pathogen-associated nucleic acids, as well as HIV, which results in more widespread cell infection. Further examination revealed that this was due to miR-126 control of plasmacytoid DC (pDC) homeostasis and function, and that miR-126 regulates expression of TLR7, TLR9, NFkB1 and other innate response genes, as well as VEGF-receptor 2 (VEGFR2). Deletion of VEGFR2 on DCs resulted in reduced interferon production, supporting a role for VEGFR2 in miR-126 regulation of pDCs. These studies identify the miR-126/VEGFR2 axis as an important regulator of the innate response that operates through multiscale control of pDCs.
Publication Title
The miR-126-VEGFR2 axis controls the innate response to pathogen-associated nucleic acids.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 29 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Tissue samples were collected from patients diagnosed with HNSCC (oropharynx, hypopharynx, larynx). Samples were taken from the tumor site (tumor samples) and from a site distant to the tumor (normal samples) prior to therapy.
Publication Title
Prognostic biomarkers for HNSCC using quantitative real-time PCR and microarray analysis: β-tubulin isotypes and the p53 interactome.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The C-terminus of CBF-SMMHC, the fusion protein produced by a chromosome 16 inversion in acute myeloid leukemia subtype M4Eo, contains domains for self-mulimerization and transcriptional repression, both of which have been proposed to be important for leukemogenesis by CBF-SMMHC. To test the role of the fusion protein's C-terminus in vivo, we generated knock-in mice expressing a C-terminally truncated CBF-SMMHC (CBF-SMMHCC95). Embryos with a single copy of CBF-SMMHCDC95 were viable and showed no defects in hematopoiesis, while embryos homozygous for the CBF-SMMHCC95 allele had hematopoietic defects and died in mid-gestation, similar to embryos with a single-copy of the full-length CBF-SMMHCC95.
Publication Title
The C-terminus of CBFβ-SMMHC is required to induce embryonic hematopoietic defects and leukemogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Dynamic transcriptional events in embryonic stem cells mediated by the super elongation complex (SEC).
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples