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SRP071090
Mus musculus
3 Downloadable Samples
Illumina HiSeq 2500
Description
Hematopoietic stem cells (HSC) sustain long-term reconstitution of hematopoiesis in primary transplantation recipients. Few HSC can serially reconstitute secondary recipients, and their identity and contribution to normal hematopoiesis remain moot. We directed transgene expression to a distinct fraction of HSC in the adult bone marrow. Epxression of the reporter transgene segregated with reconstituting activity during secondary transplantations. The labeled cells had an undifferentiated phenotype and expression profile, were slow-cycling and localized to the vascular niche. Inducible genetic labeling showed the transgene-expressing HSC gave rise to other cells within the HSC populations, confirming their top position in the differentiation hierarchy. Importantly, labeled HSC gave rise to more than two-thirds of all myeloid cells and platelets in adult mice, and this contribution could be further accelerated by interferon response. Thus, the rare "top-level" HSC with serial reconstitution capacity also serve as the major source of endogenous hematopoiesis in adult animals. Overall design: Sorted LSK CD48- CD150+ Map17-GFP+ and Map17-GFP- HSCs and LSK CD48+ CD150- Map17-GFP-MPPs were sequenced for mRNA profiling.
Publication Title
Hematopoietic Stem Cells Are the Major Source of Multilineage Hematopoiesis in Adult Animals.
Sample Metadata Fields
Cell line, Subject
View Samples- Gallus gallus
- 6 Downloadable Samples
Affymetrix Chicken Genome Array (chicken)
Description
During limb development, fibroblast growth factors (FGFs) govern proximal-distal outgrowth and patterning. FGFs also synchronize developmental patterning between the proximal-distal and anterior-posterior axes by maintaining sonic hedgehog (SHH) expression in cells of the zone of polarizing activity (ZPA) in the distal posterior mesoderm. SHH, in turn, maintains FGFs in the apical ectodermal ridge (AER) which caps the distal tip of the limb bud. Crosstalk between FGF and SHH signaling is critical for patterned limb development, but the mechanisms underlying this feedback loop are not well characterized.
Publication Title
LHX2 Mediates the FGF-to-SHH Regulatory Loop during Limb Development.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 79 Downloadable Samples
Illumina human-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Gene expression profiling-based identification of molecular subtypes in stage IV melanomas with different clinical outcome.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 57 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
Purpose: The incidence of malignant melanoma is increasing worldwide in fair-skinned populations. Melanomas respond poorly to systemic therapy, and metastatic melanomas inevitably become fatal. Although spontaneous regression, likely due to immune defense activation, rarely occurs, we lack a biological rationale and predictive markers in selecting patients for immune therapy. Experimental Design: We performed unsupervised hierarchical clustering of global gene expression data from stage IV melanomas in 57 patients. For further characterization, we used immunohistochemistry of selected markers, genome-wide DNA copy number analysis, genetic and epigenetic analysis of the Q3 CDKN2A locus, and NRAS/BRAF mutation screening. Results: The analysis revealed four distinct subtypes with gene signatures characterized by expression of immune response, pigmentation differentiation, proliferation, or stromal composition genes. Although all subtypes harbored NRAS and BRAF mutations, there was a significant difference between subtypes (P < 0.01), with no BRAF/NRAS wild-type samples in the proliferative subtype. Additionally, the proliferative subtype was characterized by a high frequency of CDKN2A homozygous deletions (P < 0.01). We observed a different prognosis between the subtypes (P = 0.01), with a particularly poor survival for patients harboring tumors of the proliferative subtype compared with the others (P = 0.003). Importantly, the clinical relevance of the subtypes was validated in an independent cohort of 44 stage III and IV melanomas. Moreover, low expression of an a priori defined gene set associated with immune response signaling was significantly associated with poor outcome (P = 0.001). Conclusions: Our data reveal a biologically based taxonomy of malignant melanomas with prognostic effect and support an influence of the antitumoral immune response on outcome.
Publication Title
Gene expression profiling-based identification of molecular subtypes in stage IV melanomas with different clinical outcome.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 22 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
Purpose: The incidence of malignant melanoma is increasing worldwide in fair-skinned populations. Melanomas respond poorly to systemic therapy, and metastatic melanomas inevitably become fatal. Although spontaneous regression, likely due to immune defense activation, rarely occurs, we lack a biological rationale and predictive markers in selecting patients for immune therapy. Experimental Design: We performed unsupervised hierarchical clustering of global gene expression data from stage IV melanomas in 57 patients. For further characterization, we used immunohistochemistry of selected markers, genome-wide DNA copy number analysis, genetic and epigenetic analysis of the Q3 CDKN2A locus, and NRAS/BRAF mutation screening. Results: The analysis revealed four distinct subtypes with gene signatures characterized by expression of immune response, pigmentation differentiation, proliferation, or stromal composition genes. Although all subtypes harbored NRAS and BRAF mutations, there was a significant difference between subtypes (P < 0.01), with no BRAF/NRAS wild-type samples in the proliferative subtype. Additionally, the proliferative subtype was characterized by a high frequency of CDKN2A homozygous deletions (P < 0.01). We observed a different prognosis between the subtypes (P = 0.01), with a particularly poor survival for patients harboring tumors of the proliferative subtype compared with the others (P = 0.003). Importantly, the clinical relevance of the subtypes was validated in an independent cohort of 44 stage III and IV melanomas. Moreover, low expression of an a priori defined gene set associated with immune response signaling was significantly associated with poor outcome (P = 0.001). Conclusions: Our data reveal a biologically based taxonomy of malignant melanomas with prognostic effect and support an influence of the antitumoral immune response on outcome.
Publication Title
Gene expression profiling-based identification of molecular subtypes in stage IV melanomas with different clinical outcome.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Changes in the transcript profile due to ABCA1 expression in murine liver samples was evaluated in LDL receptor -/- genetic backgrounds.
Publication Title
ABCA1 overexpression in the liver of LDLr-KO mice leads to accumulation of pro-atherogenic lipoproteins and enhanced atherosclerosis.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We characterized gene expression changes in the developing mouse liver at gestational days (GD) 11.5, 12.5, 13.5, 14.5, 16.5, and 19.5 and in the neonate (postnatal day (PND) 7 and 30) using full-genome microarrays and compared these changes to that in the adult liver. The fetal liver, and to a lesser extent the neonatal liver, exhibited dramatic differences in gene expression compared to adults. Canonical pathway analysis of the fetal liver signature demonstrated increases in functions important in cell replication and DNA fidelity whereas most metabolic pathways of intermediary metabolism were suppressed. Comparison of the dataset to a number of previously published datasets revealed 1) a striking similarity between the fetal liver and that of the pancreas in both mice and humans, 2) a nucleated erythrocyte signature in the fetus and 3) suppression of most xenobiotic metabolism genes throughout development, except a number of transporters associated with expression in hematopoietic cells.
Publication Title
Transcriptional ontogeny of the developing liver.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
JQ1 is a small-molecule (BET family) bromodomain inhibitor that causes a contraceptive effect in mice by blocking spermatogenesis and reducing sperm motility.
Publication Title
Small-molecule inhibition of BRDT for male contraception.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Systemic lupus erythematosous (SLE) is an autoimmune disease with an important clinical and biological heterogeneity. B lymphocytes appear central to the development of SLE which is characterized by the production of a large variety of autoantibodies and hypergammaglobulinemia. In mice, immature B cells from spontaneous lupus prone animals are able to produce autoantibodies when transferred into immunodeficient mice, strongly suggesting the existence of intrinsic B cell defects during lupus. In order to approach these defects in humans, we compared the peripheral B cell transcriptomes of quiescent lupus patients to normal B cell transcriptomes.
Publication Title
B cell signature during inactive systemic lupus is heterogeneous: toward a biological dissection of lupus.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Hematopoietic stem cells (HSCs) are identified by their ability to sustain prolonged blood cell production in vivo, although recent evidence suggests that durable self-renewal (DSR) is shared by HSC subtypes with distinct self-perpetuating differentiation programs. Net expansions of DSR-HSCs occur in vivo, but molecularly defined conditions that support similar responses in vitro are lacking. We hypothesized that this might require a combination of factors that differentially promote HSC viability, proliferation and self-renewal. We now demonstrate that HSC survival and maintenance of DSR potential is variably supported by different Steel factor (SF)-containing cocktails with similar HSC-mitogenic activities. In addition, stromal cells produce other factors, including nerve growth factor and collagen 1, that can antagonize the apoptosis of initially quiescent adult HSCs and, in combination with SF and interleukin-11, produce >15-fold net expansions of DSR-HSCs ex vivo within 7 days. These findings suggest a new molecular basis for HSC control and expansion.
Publication Title
Distinct stromal cell factor combinations can separately control hematopoietic stem cell survival, proliferation, and self-renewal.
Sample Metadata Fields
Specimen part
View Samples