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SRP034586
Homo sapiens
24 Downloadable Samples
IlluminaGenomeAnalyzerII
Description
microRNAs (miRNAs) are small noncoding RNAs that post-transcriptionally regulate gene expression by targeting specific mRNAs. Altered expression of circulating miRNAs have been associated with age-related diseases including cancer and cardiovascular disease. Although we and others have found an age-dependent decrease in miRNA expression in peripheral blood mononuclear cells (PBMCs), little is known about the role of circulating miRNAs in human aging. Here, we examined miRNA expression in human serum from young (mean age 30 years) and old (mean age 64 years) individuals using next generation sequencing technology and real-time quantitative PCR. Of the miRNAs that we found to be present in serum, three were significantly decreased in 20 older individuals compared to 20 younger individuals: miR-151a-5p, miR-181a-5p and miR-1248. Consistent with our data in humans, these miRNAs are also present at lower levels in the serum of elderly rhesus monkeys. In humans, miR-1248 was found to regulate the expression of mRNAs involved in inflammatory pathways and miR-181a was found to correlate negatively with the pro-inflammatory cytokines IL-6 and TNFa and to correlate positively with the anti-inflammatory cytokines TGFb and IL-10. These results suggest that circulating miRNAs may be a biological marker of aging and could also be important for regulating longevity. Identification of stable miRNA biomarkers in serum could have great potential as a noninvasive diagnostic tool as well as enhance our understanding of physiological changes that occur with age. Overall design: Examination of microRNAs isolated from human serum from 11 young (mean age 30 yrs) and 11 old (mean age 64 yrs) individuals and from peripheral blood mononuclear cells from one young (30 yr) and one old (64 yr) individual.
Publication Title
Age-related changes in microRNA levels in serum.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 23 Downloadable Samples
- Ion Torrent Proton
Description
Circulating extracellular RNAs (exRNAs) are potential biomarkers of disease. We thus hypothesized that age-related changes in exRNAs can identify age-related processes. We profiled both large and small RNAs in human serum to investigate changes associated with normal aging. exRNA was sequenced in 13 young (30-32 yrs.) and 10 old (80-85 yrs.) African American women to identify all RNA transcripts present in serum. We identified age-related differences in several RNA biotypes, including mitochondrial transfer RNAs, mitochondrial ribosomal RNA, and unprocessed pseudogenes. Age-related differences in unique RNA transcripts were further validated in an expanded cohort. Pathway analysis revealed that EIF2 signaling, oxidative phosphorylation, and mitochondrial dysfunction were among the top pathways shared between young and old. Protein interaction networks revealed distinct clusters of functionally-related protein-coding genes in both age-groups. These data provide timely and relevant insight into the exRNA repertoire in serum and its change with aging. Overall design: Profiling of extracellular RNA (exRNA) from human serum in 13 young (30.9 ± 0.60 yrs) and 10 old (81.8 ± 1.87 yrs) individuals.
Publication Title
Extracellular RNA profiles with human age.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Malat1 is not an essential component of nuclear speckles in mice.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Malat1 is an abundant long noncoding RNA that localizes to nuclear bodies known as nuclear speckles, which contain a distinct set of pre-mRNA processing factors. Previous in vitro studies have demonstrated that Malat1 interacts with pre-mRNA splicing factors, including the serine- and arginine-rich (SR) family of proteins, and regulates a variety of biological processes, including cancer cell migration, synapse formation, cell cycle progression, and responses to serum stimulation. To address the physiological function of Malat1 in a living organism, we generated Malat1-KO (KO) mice using homologous recombination. Unexpectedly, the Malat1-KO mice were viable and fertile, showing no apparent phenotypes. Nuclear speckle markers were also correctly localized in cells that lacked Malat1. However, the cellular levels of another long noncoding RNA, Neat1, which is an architectural component of nuclear bodies known as paraspeckles, were downregulated in a particular set of tissues and cells lacking Malat1.
Publication Title
Malat1 is not an essential component of nuclear speckles in mice.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 32 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Rhabdomyosarcoma is a pediatric malignancy thought to arise from the uncontrolled proliferation of myogenic cells. Here, we have generated models of rhabdomyosarcoma in the zebrafish by inducing oncogenic KRASG12D expression at different stages during muscle development. Several zebrafish promoters were used including the cdh15 and rag2 promoters that drive gene expression in early muscle progenitors, and the mylz2 promoter that expresses in differentiating myoblasts. The tumors that developed differed in their ability to recapitulate normal myogenesis. cdh15:KRASG12D and rag2:KRASG12D fish developed tumors that displayed an inability to fully undergo muscle differentiation by histologic appearance and gene expression analyses. In contrast, mylz2:KRASG12D tumors more closely resembled mature skeletal muscle and were most similar to well-differentiated human rhabdomyosarcoma by gene expression. mylz2:KRASG12D fish showed significantly improved survival compared to cdh15:KRASG12D and rag2:KRASG12D fish. Tumor-propagating activity was enriched in myf5-expressing cell populations within all of the tumor types. Our results demonstrate that oncogene expression at different stages during muscle development has profound effects on the ability of tumor cells to recapitulate normal myogenesis, altering the tumorigenic capability of these cells.
Publication Title
Zebrafish rhabdomyosarcoma reflects the developmental stage of oncogene expression during myogenesis.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 9 Downloadable Samples
- Zebrafish Gene 1.0 ST Array (zebgene10st)
Description
Key regulators of septum formation between the left and right ventricle in mammals, including the transcription factors TXB5 and PITX2, feature loss-of-function phenotypes that affect development of the two-chambered zebrafish heart, suggesting
Publication Title
Generating and evaluating a ranked candidate gene list for potential vertebrate heart field regulators.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 18 Downloadable Samples
- Zebrafish Gene 1.0 ST Array (zebgene10st)
Description
The zebrafish is a powerful model for the study of hematopoietic stem and progenitor cells (HSPC). We have developed a novel HSPC-specific transgenic line (Runx1+23:GFP). We have used this line in time-lapse live imaging studies to track the migration of HSPC during development. We have also performed a chemical genetic screen to find small molecules that modulate HSPC numbers during development. Treating embryos from 2-3 days post fertilization (2-3 dpf) then fixing for in situ staining with HSPC probes cmyb and runx1, we found the compound lycorine increased HSPC numbers. Applying this compound during time-lapse live imaging showed increased accumulation of Runx+ HSPC in the caudal hematopoietic tissue (CHT). Treatment from 2-3 dpf, then washing off the compound, had a sustained effect on the size of the HSPC with Runx+ numbers higher at 5 and 7 dpf.
Publication Title
Hematopoietic stem cell arrival triggers dynamic remodeling of the perivascular niche.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Activation or maintenance of a leukemia stem cell self-renewal pathway in downstream myeloid cells is an important component of AML development
Publication Title
The Wnt/beta-catenin pathway is required for the development of leukemia stem cells in AML.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 8 Downloadable Samples
- IlluminaHiSeq2500
Description
Goal of this study is differential gene expression between wild type and Toddler mutant during early zebrafish embryogenesis Overall design: Four timepoints - 4 hours post fertilization (hpf), 5 hpf, 6 hpf, and 7 hpf; one replicate of wild type at each time point, one replicate Toddler mutant at each time point
Publication Title
Toddler signaling regulates mesodermal cell migration downstream of Nodal signaling.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We aimed to investigate the function of syndecan-1 in tumor cell adhesion and migration, with special focus on the importance of its distinct protein domains, to better understand the structure-function relationship of syndecan-1 in tumor progression. We utilized two mesenchymal tumor cell lines which were transfected to stably overexpress full-length syndecan-1 or truncated variants: the 78 which lacks the extracellular domain except the DRKE sequence proposed to be essential for oligomerization, the 77 which lacks the whole extracellular domain, and the RMKKK which serves as a nuclear localization signal. Various bioassays for cell adhesion, chemotaxis, random movement and wound healing were studied. Furthermore we performed gene microarray to analyze the global gene expression pattern influenced by syndecan-1.
Publication Title
Novel genes and pathways modulated by syndecan-1: implications for the proliferation and cell-cycle regulation of malignant mesothelioma cells.
Sample Metadata Fields
No sample metadata fields
View Samples