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SRP134175
Drosophila melanogaster
9 Downloadable Samples
Illumina HiSeq 2500
Description
Mammalian insulin and IGF induce similar but not identical changes in gene expression downstream of their respective receptors. Signaling bias at the receptor differentiates the two similar ligands, though the precise mechanism is not entirely understood. We used Drosophila insulin-like peptides DILP2 and DILP5 to determine how similar insulin-like ligands regulate similar and distinct patterns of gene expression in S2 cells by RNA-Seq. Overall, DILP2 and DILP5 stimulate many of the same changes in gene expression. However, some genes are uniquely regulated by DILP2 or by DILP5. Shared and distinct gene targets were validated by q-RT-PCR with indepedent replicates. Some unique gene targets of DILP2 are involved in sugar metabolism, which is functionally related in vivo to DILP2 and not DILP5. We find that gene expression is largely regulated in parallel by DILP2 and DILP5 but some key unique targets may lead to differential physiological functions for the two insulin-like genes. Overall design: mRNA profiles from S2 cells treated with DILP2, DILP5 or solvent were sequenced on an Illumina HiSeq2500
Publication Title
<i>Drosophila</i> Insulin-Like Peptides DILP2 and DILP5 Differentially Stimulate Cell Signaling and Glycogen Phosphorylase to Regulate Longevity.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Schizosaccharomyces pombe
- 16 Downloadable Samples
Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Transition from proliferation to quiescence brings about extensive changes in cellular behavior and structure. However, genes critical for establishing and/or for maintaining quiescence are largely unknown. The fission yeast S. pombe is found as an excellent model for studying this problem, because it becomes quiescent under nitrogen starvation. Here we characterize 610 temperature-sensitive (ts) mutants, and identify 33 genes required for entry into and the maintenance of quiescence. These genes cover a broad range of cellular functions in the cytoplasm, membrane and the nucleus, encoding proteins for stress-responsive and cell cycle kinase signaling pathway, actin-bound and osmo-controlling endosome formation, RNA transcription, splicing and ribosome biogenesis, chromatin silencing, biosynthesis of lipid and ATP, cell wall and membrane morphogenesis, protein trafficking and vesicle fusion. We specifically highlight Fcp1, CTD phosphatase of RNA polymerase II, which differentially affects transcription of genes involved in quiescence and proliferation. We propose that the transcriptional role of Fcp1 is central to differentiate quiescence from proliferation.
Publication Title
Genetic control of cellular quiescence in S. pombe.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Papillary thyroid cancers (PTC) that invade into local structures are associated with a poor prognosis, but the mechanisms for PTC invasion are incompletely defined limiting the development of new therapies. To characterize biological processes involved in PTC invasion, we analyzed the gene expression profiles of microscopically dissected intratumoral samples from central and invasive regions of seven widely invasive PTCs and normal thyroid tissue by oligonucleotide microarray and performed confirmatory expression and functional studies. In comparison to the central regions of primary PTCs, the invasive fronts overexpressed TGFbeta, NFkappaB and integrin pathway members, and regulators of small G-proteins and CDC42. Moreover, reduced levels of mRNAs encoding proteins involved in cell-cell adhesion and communication were identified, consistent with epithelial-to-mesenchymal transition (EMT). To confirm that aggressive PTCs were characterized by EMT, 35 additional PTCs were examined for expression of vimentin, a hallmark of EMT. Overexpression of vimentin was associated with PTC invasion and nodal metastasis. Functional, in vitro studies demonstrated that vimentin was required for the development and maintenance of both a mesenchymal morphology and invasiveness in thyroid cancer cells. We conclude that EMT is a common mechanism of PTC invasion and that vimentin regulates thyroid cancer EMT in vitro.
Publication Title
Gene expression and functional evidence of epithelial-to-mesenchymal transition in papillary thyroid carcinoma invasion.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina Genome Analyzer II
Description
Autosomal-recessive loss of the NSUN2 gene has been recently identified as a causative link to intellectual disability disorders in humans. NSun2 is an RNA methyltransferase modifying cytosine-5 in transfer RNAs (tRNA). Whether NSun2 methylates additional RNA species is currently debated. Here, we adapted the individual-nucleotide resolution UV cross-linking and immunoprecipitation method (iCLIP) to identify NSun2-mediated methylation in RNA transcriptome. We confirm site-specific methylation in tRNA and identify messenger and non-coding RNAs as potential methylation targets for NSun2. Using RNA bisulfite sequencing we establish Vault non-coding RNAs as novel substrates for NSun2 and identified six cytosine-5 methylated sites. Furthermore, we show that loss of cytosine-5 methylation in Vault RNAs causes aberrant processing into argonaute-associating small RNA fragments (svRNA). Thus, impaired Vault non-coding RNA processing may be an important contributor to the etiology of NSUN2-deficieny human disorders. Overall design: mRNA-seq in Embryonic kidney (HEK293) cells transfected with siRNA against Nsun2 vs control
Publication Title
NSun2-mediated cytosine-5 methylation of vault noncoding RNA determines its processing into regulatory small RNAs.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 64 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
The inner ear in mammals is derived from a simple ectodermal thickening called the otic placode. Through a series of complex morphological changes, the placode forms the mature inner ear comprising of the auditory organ (cochlea) and the vestibular/balance organs (utricle, saccule, and three semi-circular canals). The vast majority of genes known to be involved during inner ear development have been found through mutational screens or by chance.
Publication Title
Toward a systems biology of mouse inner ear organogenesis: gene expression pathways, patterns and network analysis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Several transcription factors are known to be expressed in discrete regions of the otic vesicle and Dlx5 is one of those that is expressed highly in the presumptive dorsal vestibular region. Mice lacking Dlx5 have vestibular defects. Specifically, they fail to form the endolymphatic duct (a defect visible as early as E10) as well as the anterior and posterior semi-circular canals. The lateral canal does form but is smaller, whereas the saccule, the utricle and the cochlea appear relatively normal. The goal of this study was to use microarrays to identify differentially expressed genes between wild-type and Dlx5-null otic vesicles microdissected from E10 and 10.5 and identify downstream targets of Dlx5 by searching the immediate 3kb promoter regions of the differentially expressed genes for homeodomain binding sites followed by chromatin immunoprecipitation in an otic vesicle-derived cell line over-expressing Dlx5.
Publication Title
Identification of direct downstream targets of Dlx5 during early inner ear development.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Continuous stress caused by smoking induces changes in the cell population of small airway epithelium, with basal cell hyperplasia and goblet cell metaplasia at the expense of ciliated cells, and there is now compiling evidence that basal cells play a key role in the early pathogenesis of Chronic Obtructive Pulmonary Disease (COPD).
Publication Title
Microarray analysis identifies defects in regenerative and immune response pathways in COPD airway basal cells.
Sample Metadata Fields
Specimen part, Disease stage
View Samples- Homo sapiens
- 54 Downloadable Samples
- Illumina HiSeq 2500
Description
Human lymphoid tissues harbor, in addition to CD56bright and CD56dim natural killer (NK) cells, a third NK cell population: CD69+CXCR6+ lymphoid tissue (lt)NK cells. The function and development of ltNK cells remain poorly understood. In this study we performed RNA sequencing on the CD56bright and CD56dim NK cells (from bone marrow and blood), and the ltNK cells (from bone marrow). In addition, the blood derived CD56dim, and bone marrow derived ltNK cells were further subdivided into a NKG2A+ and NKG2A- fraction. Paired blood and bone marrow samples of 4 healthy donors were included. When comparing the NKG2A fractions, only 3 genes (of 9382 genes included) had a significantly differential expression. Therefore, we pooled the expression data proportionally from the NKG2A+ and NKG2A- fractions in subsequent analyses. In ltNK cells, 1353 genes were differentially expressed compared to circulating NK cells. Several molecules involved in migration were downregulated in ltNK cells: S1PR1, SELPLG and CD62L. By flow cytometry we confirmed that the expression profile of adhesion molecules (CD49e-, CD29low, CD81high, CD62L-, CD11c-) and transcription factors (Eomeshigh, Tbetlow) of ltNK cells differed from their circulating counterparts. LtNK cells were characterized by enhanced expression of inhibitory receptors TIGIT and CD96 and low expression of DNAM1 and cytolytic molecules (GZMB, GZMH, GNLY). Their proliferative capacity was reduced compared to the circulating NK cells. By performing gene set enrichment analysis we identified DUSP6 and EGR2 as potential regulators of the ltNK cell transcriptome. Remarkably, comparison of the ltNK cell transcriptome to the published human spleen-resident memory CD8+ T (Trm) cell transcriptome revealed an overlapping gene signature. Moreover, the phenotypic profile of ltNK cells resembled that of CD8+ Trm cells in bone marrow. Together, we provide a comprehensive molecular framework of the conventional CD56bright and CD56dim NK cells as well as the tissue-resident ltNK cells and provide a core gene signature which might be involved in promoting tissue-residency. Overall design: mRNA sequencing of NK cell populations isolated from blood: CD56bright, NKG2A+ CD56dim and NKG2A- CD56dim, and bone marrow: CD56bright, CD56dim, NKG2A+ ltNK, and NKG2A- ltNK. Each sample has 4 biological replicates.
Publication Title
Human Bone Marrow-Resident Natural Killer Cells Have a Unique Transcriptional Profile and Resemble Resident Memory CD8<sup>+</sup> T Cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The objective of this study is to assess the effects of the Serum Response Factor deletion on the cardiac gene expression program at different time points after the deletion (day 8 and day 25) and to compare the response of SRF-deficient heart and control heart to phenylephrine, an alpha-adrenergic agonist triggering cardiac hypertrophy.
Publication Title
Nicotinamide Riboside Preserves Cardiac Function in a Mouse Model of Dilated Cardiomyopathy.
Sample Metadata Fields
Sex
View Samples