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SRP119595
Mus musculus
10 Downloadable Samples
Illumina HiSeq 1500
Description
STING plays a key role in detecting cytosolic DNA and induces type I interferon responses for host defense against pathogens. Although T cells highly express STING, its physiological role remains unknown. In this study, we show that costimulation of T cells via TCR and STING ligand induce type I IFN responses like innate immune cells. Overall design: Naïve CD4+ T cells were stimulated with anti-CD3/28 in the presence or absence of STING ligand and analyzed the transcriptome using Illumina HiSeq1500.
Publication Title
Reciprocal regulation of STING and TCR signaling by mTORC1 for T-cell activation and function.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Histone methyltransferase DOT1L coordinates AR and MYC stability in prostate cancer.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
We performed expression profiling of prostate cancer cells, LNCaP and PC3 cells that were treated with the specific DOT1L inhibitor EPZ004777 (1uM) for 8 days. We found that unique genes were differentially expressed in both cell lines.
Publication Title
Histone methyltransferase DOT1L coordinates AR and MYC stability in prostate cancer.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The transcription factor Meis1 is preferentially expressed in hematopoietic stem cells (HSCs) and over-expressed in certain leukemias. However, the functions of Meis1 in hematopoiesis remain largely unknown. Using inducible knock-out mice, we found that Meis1 is required for the maintenance of hematopoiesis under stress and over long term while steady-state hematopoiesis was sustained in the absence of Meis1. Bone marrow cells of Meis1 deficient mice showed reduced colony formation, contained significantly fewer numbers of long- term HSCs and these Meis1-deficient HSCs exhibited loss of quiescence. Further, we found that Meis1 deletion led to the accumulation of reactive oxygen species (ROS) in HSCs and decreased expression of genes implicated in hypoxia response. Finally, ROS scavenging by N-acetyl cysteine or stabilization of hypoxia-signaling by knockdown of the VHL protein led to reversal of the effects of Meis1-deletion. Taken together, these results demonstrate that Meis1 protects and preserves HSCs by restricting oxidative metabolism.
Publication Title
Meis1 preserves hematopoietic stem cells in mice by limiting oxidative stress.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Patients with bicuspid aortic valve (BAV) have increased risk of thoracic ascending aortic aneurysm (AscAA) and dissection compared to those with a normal tricuspid aortic valve (TAV). The present study was undertaken to evaluate whether differences in gene expression exist in aortas from BAV and TAV patients with AscAA.
Publication Title
Elevated expressions of osteopontin and tenascin C in ascending aortic aneurysms are associated with trileaflet aortic valves as compared with bicuspid aortic valves.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
- NextSeq 500
Description
Mutations in the RNA splicing complex member SRSF2 are found frequently in myelodysplastic syndrome and related malignancies such as chronic myelomonocytic leukemia. These mutations cluster on proline 95, with P95H the most frequent. How SRSF2P95H mutations modify hematopoiesis and promote MDS/MPN development is not clear. We have established a conditionally activatable Srsf2P95H/+ knock-in allele which, when expressed within the hematopoietic stem cell populations caused profound myeloid bias, at the expense of erythroid and lymphoid cells, and a reduced frequency and competitive repopulation of HSCs. Long-term aging of Srsf2P95H/+ resulted in the development of MDS/MPN characterised by myeloid dysplasia and monocytosis. Reproducible key phenotypic features make this a mouse model suitable for mechanistic and preclinical MDS sudies. Overall design: RNAseq of whole bone marrow in vivo tamoxifen treated R26CreERT2 Srsf2 P95H generated by deep sequencing, using Illumina NextSeq500
Publication Title
<i>Srsf2</i><i><sup>P95H</sup></i> initiates myeloid bias and myelodysplastic/myeloproliferative syndrome from hemopoietic stem cells.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
The pathogenesis of MLL-fusion gene leukemias has been linked to upregulated expression of HOX genes and of the HOX-cofactor Meis1.The functions of the HOX/MEIS1 complex in leukemia however remain unclear. Here, we used inducible MEIS1-knockout mice coupled with MLL-AF9 knockin mice to decipher the role of MEIS1 in leukemia. We found that MEIS1 was critically required for established leukemia. Further, MEIS1 loss led to increased oxygen flux and apoptosis, while hypoxia reversed these effects. Finally, we identify HLF as a downstream mediator of MEIS1 in leukemia. Overexpression of HLF prevents oxygen flux and rescues the leukemia phenotype in MEIS1-deficient cells. Thus, the oncogenic effects of MEIS1 are at least partly mediated by an HLF-driven hypoxic state. Overall design: Mouse bone marrow MLL-AF9 knockin cells of conditional Meis1f/f or control genotypes were treated with vehicle or 1000 nM of 4-hydroxy tamoxifen for 24 hours in IMDM with 10% FBA and 10 ng/ml of murine GM-CSF, IL-3, IL-6, SCF. RNA was isolated from treated cells and submitted to gene expression and sequencing core of Cincinnati Children''s Hospital & Medical Center. A total of four samples were included, and two groups were assisgned. Comparison comprises mRNA expression profile of vehicle and 4-OHT treatment in control cells versus Meis1-deleted cells.
Publication Title
MEIS1 regulates an HLF-oxidative stress axis in MLL-fusion gene leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 14 Downloadable Samples
- IlluminaHiSeq2000
Description
High expression of the ETS family transcription factor ERG is associated with poor clinical outcome in acute myeloid leukemia (AML) and acute T-cell lymphoblastic leukemia (T-ALL). In murine models, high ERG expression induces both T-ALL and AML. However, no study to date has defined the effect of high ERG expression on primary human hematopoietic cells. In the present study, human CD34+ cells were transduced with retroviral vectors to elevate ERG gene expression to levels detected in high ERG AML. RNA sequencing was performed on purified populations of transduced cells to define the effects of high ERG on gene expression in human CD34+ cells. Integration of the genome-wide expression data with other data sets revealed that high ERG drives an expression signature that shares features of normal hematopoietic stem cells, high ERG AMLs, early T-cell precursor-ALLs and leukemic stem cell signatures associated with poor clinical outcome. Functional assays linked this gene expression profile to enhanced progenitor cell expansion. These results support a model whereby a stem cell gene expression network driven by high ERG in human cells enhances the expansion of the progenitor pool, providing opportunity for the acquisition and propagation of mutations and the development of leukemia. Overall design: RNA sequencing in ERG overexpressing human CD34+ cells
Publication Title
Overexpression of ERG in cord blood progenitors promotes expansion and recapitulates molecular signatures of high ERG leukemias.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
- Illumina HiSeq 2000
Description
Different combinations of Endoglin tissue specific enhancers define hemangioblast and hemogenic endothelium cell fractions Overall design: We generated a series of embryonic stem cell lines, each targeted with reporter constructs driven by tissue specific promoter/enhancer combinations of Endoglin (ENG). The Eng promoter (P) when combined with the -8/+7/+9kb enhancers targeted cells in FLK1 mesoderm that were enriched for blast colony forming potential, whereas the P/-8kb enhancer targeted TIE2+/c-KIT+/CD41- HE cells that were enriched for hematopoietic potential. These cell fractions were isolated and their transcriptomes profiled by RNA-seq.
Publication Title
Identification of novel regulators of developmental hematopoiesis using Endoglin regulatory elements as molecular probes.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 33 Downloadable Samples
- IlluminaHiSeq2000
Description
RNA-seq of bone marrow CD34+ cells of myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) patients to identify at the molecular pathways involved in primary resistance to AZA therapy. Overall design: RNA-seq of bone marrow CD34+ cells of MDS and CMML patients at pre-treatment and after 6 cycles of AZA treatment to identify at the molecular pathways involved in resistance to AZA therapy.
Publication Title
Integrative Genomics Identifies the Molecular Basis of Resistance to Azacitidine Therapy in Myelodysplastic Syndromes.
Sample Metadata Fields
No sample metadata fields
View Samples