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SRP009919
Mus musculus
9 Downloadable Samples
Illumina Genome Analyzer II
Description
We used transgenic mouse embryos that are deficient in the two enzymatically active RNA editing enzymes ADAR1 and ADAR2 to compare relative frequencies but also sequence composition of mature miRNAs in these genetically modified backgrounds to wild-type mice by Illumina next gen sequencing. Deficiency of ADAR2 leads to a reproducible change in abundance of specific miRNAs and their predicted targets. Changes in miRNA abundance seem unrelated to editing events. Additional deletion of ADAR1 has surprisingly little impact on the mature miRNA repertoire, indicating that miRNA expression is primarily dependent on ADAR2. A to G transitions reflecting A to I editing events can be detected at few sites and at low frequency during the early embryonic stage investigated. Again, most editing events are ADAR2 dependent with only few editing sites being specifically edited by ADAR1. Besides known editing events in miRNAs a few novel, previously unknown editing events were identified. Some editing events are located to the seed region of miRNAs opening the possibility that editing leads to their retargeting. Overall design: GSM852140-8: sequencing of mature miRNAs of wt, ADAR2-/- and ADAR1-/-/ADAR2-/- female mouse embryos at E11.5 GSM863778-81: Gene expression was measured in wiltype, ADAR2-/- and ADAR1-/-/ADAR2-/- E11.5 whole female mouse embryos using Agilent Whole Mouse Genome Oligo Microarrays 8x60K.
Publication Title
Adenosine deaminases that act on RNA induce reproducible changes in abundance and sequence of embryonic miRNAs.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Tumor metastasis and lack of NKG2D ligand (NKG2DL) expression are associated with poor prognosis in patients with colon cancer. Here we found that spironolactone (SPIR), an FDA-approved diuretic drug with a long-term safety profile, can upregulate NKG2DL expression in multiple colon cancer cell lines by activating the ATM-Chk2-mediated checkpoint pathway, which in turn enhances tumor elimination by natural killer cells. SPIR can also upregulate the expression of metastasis-suppressor genes TIMP2 and TIMP3, thereby reducing tumor cell invasiveness. Although SPIR is an aldosterone antagonist, its anti-tumor effects are independent of the mineralocorticoid receptor pathway. Instead, by screening the human nuclear hormone receptor siRNA library, we identify retinoid X receptor gamma (RXR gamma) as being indispensable for the anti-tumor functions of SPIR. Collectively, our results strongly support the use of SPIR or other RXR gamma-agonists with minimal side effects for colon cancer prevention and therapy.
Publication Title
Modulation of NKG2D ligand expression and metastasis in tumors by spironolactone via RXRγ activation.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st), Illumina Genome Analyzer II
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
ADAR2 induces reproducible changes in sequence and abundance of mature microRNAs in the mouse brain.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st), Illumina Genome Analyzer II
Description
Background: Adenosine deaminases that act on RNA (ADARs) bind to double-stranded and structured RNAs and deaminate adenosines to inosines. This A to I editing is widespread and required for normal life and development. Besides mRNAs and repetitive elements, ADARs can target miRNA precursors. Editing of miRNA precursors can affect processing efficiency and alter target specificity. Interestingly, ADARs can also influence miRNA abundance independent of RNA-editing. In mouse embryos where editing levels are low, ADAR2 was found to be the major ADAR protein that affects miRNA abundance. Here we extend our analysis to adult mouse brains where high editing levels are observed.
Publication Title
ADAR2 induces reproducible changes in sequence and abundance of mature microRNAs in the mouse brain.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
DNA methylation is the net result of deposition by DNA methyltransferases (DNMT1, 3A and 3B) and removal by the Ten-Eleven Translocation 1-3 (TET1-3) family of proteins and/or passive loss by replication. The relative contribution of the individual enzymes and pathways is only partially understood. Here we comprehensively analyzed and mathematically simulated the dynamics of DNA de-methylation during the reprogramming of the hypermethylated serum-cultured mouse embryonic stem cells (ESCs) to the hypomethylated 2i-cultured ground state of mESC. We show that DNA demethylation readily occurs in TET[1-/-, 2-/-] ESCs with similar kinetics as their WT littermates. Vitamin C activation of TET causes accelerated and more profound DNA demethylation without markedly affecting reprogramming kinetics. We developed a mathematical model that highly accurately predicts the global level of 5methyl- and 5hydroxymethylcytosine during the transition. Modeling and experimental validation show that the concentration of DNMT3A and DNMT3B determines the steady state level of global DNA methylation and absence of DNMT3A/B even in continued presence of DNMT1 results in gradual loss of 5mC. Taken together, DNMT1 alone is insufficient to maintain DNA methylation but requires the action of DNMT3A/3B that act as a “dimmer switches”. Overall design: RNA-seq time series was performed during the early time phase of serum to 2i transition in the presence and absence of vitamin C (4h, 16h,24h, 32h), 1 replicate
Publication Title
Impairment of DNA Methylation Maintenance Is the Main Cause of Global Demethylation in Naive Embryonic Stem Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To identify cellular and genetic abnormalities involved in interstrand cross link repair-deficient bone marrow failure and its transformation to leukemia, we used an Ercc1 hypomorphic mouse model (Ercc1 -/d).
Publication Title
ICL-induced miR139-3p and miR199a-3p have opposite roles in hematopoietic cell expansion and leukemic transformation.
Sample Metadata Fields
Age, Specimen part
View Samples- Rattus norvegicus
- 18 Downloadable Samples
- Affymetrix Rat Gene 2.1 ST Array (ragene21st)
Description
Accute stretch and tachycardia are capable of inducing pathological excitation transcription coupling - an early invent before structural cardiac remodeling which transitions to heart failure. The sodium calcium exchanger is a key player in maintaining calcium homeostasis and is implicated in pathological signaling during heart failure.
Publication Title
The role of stretch, tachycardia and sodium-calcium exchanger in induction of early cardiac remodelling.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 117 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Apo2L/TRAIL stimulates cancer-cell death through the proapoptotic receptors DR4 and DR5, but the determinants of tumor susceptibility to this ligand are not fully defined. mRNA expression of the peptidyl O-glycosyl transferase GALNT14 correlated with Apo2L/TRAIL sensitivity in pancreatic carcinoma, non-small cell lung carcinoma and melanoma cell lines (P < 0.00009; n=83), and up to 30% of samples from various human malignancies displayed GALNT14 overexpression. RNA interference of GALNT14 reduced cellular Apo2L/TRAIL sensitivity, whereas overexpression increased responsiveness. Biochemical analysis of DR5 identified several ectodomain O-GalNAc-Gal-Sialic acid structures. Sequence comparison predicted conserved extracellular DR4 and DR5 O-glycosylation sites; progressive mutation of the DR5 sites attenuated apoptosis signaling. O-glycosylation promoted ligand-stimulated clustering of DR4 and DR5, which mediated recruitment and activation of the apoptosis-initiating protease caspase-8. These results uncover a novel link between death receptor O-glycosylation and apoptosis signaling, providing potential predictive biomarkers for Apo2L/TRAIL-based cancer therapy.
Publication Title
Death-receptor O-glycosylation controls tumor-cell sensitivity to the proapoptotic ligand Apo2L/TRAIL.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 16 Downloadable Samples
- NextSeq 500
Description
Adult Stem Cell (ASC )-derived organoids are 3D epithelial structures that recapitulate essential aspects of their organ of origin. We have developed conditions for the long-term growth of primary kidney tubular epithelial organoids ('tubuloids'). Cultures can be established from mouse and human kidney tissue, as well as from urine and can be expanded for at least 20 passages (> 6 months). The structures retain a normal number of chromosomes. Human tubuloids represent proximal as well as distal nephron segments, as evidenced by gene expression, immunofluorescence and tubular functional analyses. BK virus infection of tubuloids recapitulates in vivo phenomena. "Tumoroids" can be established from Wilms nephroblastoma. Kidney tubuloids from urine from a subject with Cystic Fibrosis (CF) allows ex vivo assessment of treatment efficacy. Finally, tubuloids cultured on microfluidic organ-on-a-chip plates adopt a tubular conformation and display active (trans-)epithelial transport function. Adult kidney-derived epithelial tubuloids allow studies of hereditary, infectious and malignant kidney disease in a personalized fashion. Overall design: We generated single cell transcriptome data of kidney tubuloids and the tissue that the tubuloids were derived from
Publication Title
Tubuloids derived from human adult kidney and urine for personalized disease modeling.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- NextSeq 500
Description
Adult Stem Cell (ASC )-derived organoids are 3D epithelial structures that recapitulate essential aspects of their organ of origin. We have developed conditions for the long-term growth of primary kidney tubular epithelial organoids ('tubuloids'). Cultures can be established from mouse and human kidney tissue, as well as from urine and can be expanded for at least 20 passages (> 6 months). The structures retain a normal number of chromosomes. Human tubuloids represent proximal as well as distal nephron segments, as evidenced by gene expression, immunofluorescence and tubular functional analyses. BK virus infection of tubuloids recapitulates in vivo phenomena. "Tumoroids" can be established from Wilms nephroblastoma. Kidney tubuloids from urine from a subject with Cystic Fibrosis (CF) allows ex vivo assessment of treatment efficacy. Finally, tubuloids cultured on microfluidic organ-on-a-chip plates adopt a tubular conformation and display active (trans-)epithelial transport function. Adult kidney-derived epithelial tubuloids allow studies of hereditary, infectious and malignant kidney disease in a personalized fashion. Overall design: We generated transcriptome data of kidney tubuloids and the tissue that the tubuloids were derived from
Publication Title
Tubuloids derived from human adult kidney and urine for personalized disease modeling.
Sample Metadata Fields
Specimen part, Subject
View Samples