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SRP063833
Mus musculus
7 Downloadable Samples
Illumina HiSeq 2000
Description
The Mdm2 oncoprotein ubiquitinates and antagonizes p53 but may also carry out p53-independent functions. Here we report that Mdm2 is required for the efficient generation of induced pluripotent stem cells (iPSCs) from murine embryonic fibroblasts, in the absence of p53. Similarly, Mdm2 depletion in the context of p53 deficiency also promoted the differentiation of human mesenchymal stem cells and diminished clonogenic survival of cancer cells. Most of the Mdm2-controlled genes also responded to the inactivation of the Polycomb Repressor Complex 2 (PRC2) and its catalytic component EZH2. Mdm2 physically associated with EZH2 on chromatin, enhancing the trimethylation of Histone 3 at lysine 27 and the ubiquitination of Histone 2A at lysine 119 (H2AK119) at its target genes. Removing Mdm2 simultaneously with the H2AK119 E3 ligase Ring1B/RNF2 further induced these genes and synthetically arrested cell proliferation. In conclusion, Mdm2 supports the Polycomb-mediated repression of lineage specific genes independent of p53. Overall design: Expression profiling by high throughput sequencing of p53 ko MEFs, p53Mdm2 ko MEFs, p53ko Mdm2 C462A ki MEFs.
Publication Title
MDM2 Associates with Polycomb Repressor Complex 2 and Enhances Stemness-Promoting Chromatin Modifications Independent of p53.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
Conversion of fibroblasts to functional cardiomyocytes represents a potential approach for restoring cardiac function following myocardial injury, but the technique thus far has been slow and inefficient. To improve the efficiency of reprogramming fibroblasts to cardiac-like myocytes (iCMs) by cardiac transcription factors (Gata4, Hand2, Mef2c, and Tbx5=GHMT), we screened 192 protein kinases and discovered that Akt/protein kinase B dramatically accelerates and amplifies this process. Approximately 50% of reprogrammed fibroblasts displayed spontaneous beating after three weeks of induction by Akt plus GHMT. Furthermore, addition of Akt1 to GHMT evoked a more mature cardiac phenotype for iCMs, as seen by enhanced polynucleation, cellular hypertrophy, gene expression, and metabolic reprogramming. Igf1 and Pi3 kinase acted upstream of Akt, whereas mTORC1 and Foxo3a acted downstream of Akt to influence fibroblast-to-cardiomyocyte reprogramming. These findings provide new insights into the molecular basis of cardiac reprogramming and represent an important step toward further application of this technique. Overall design: We performed RNA-Seq using either isolated adult mouse ventricular cardiomyocytes (CMs) or MEFs treated for three weeks with empty vector, GHMT (iCMs cell sorted using aMHC-GFP before RNA-Seq), or AGHMT (iCMs cell sorted using aMHC-GFP before RNA-Seq).
Publication Title
Akt1/protein kinase B enhances transcriptional reprogramming of fibroblasts to functional cardiomyocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
Illumina MouseRef-8 v2.0 expression beadchip
Description
Identify genes like Ifit1 which are induced in L929 cells but not L929 cells expressing ectopic IRF8
Publication Title
Interferon Regulatory Factor 8 (IRF8) Impairs Induction of Interferon Induced with Tetratricopeptide Repeat Motif (IFIT) Gene Family Members.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 20 Downloadable Samples
- IlluminaHiSeq1000, IlluminaGenomeAnalyzerIIx
Description
Altered daily patterns of hormone action are suspected to contribute to metabolic disease. It is poorly understood how the adrenal glucocorticoid hormones contribute to the coordination of daily global patterns of transcription and metabolism. Here, we examined diurnal metabolite and transcriptome patterns in a zebrafish glucocorticoid deficiency model by RNA-Seq, NMR spectroscopy and liquid chromatography-based methods. We observed dysregulation of metabolic pathways including glutaminolysis, the citrate and urea cycles and glyoxylate detoxification. Constant, non-rhythmic glucocorticoid treatment rescued many of these changes, with some notable exceptions among the amino acid related pathways. Surprisingly, the non-rhythmic glucocorticoid treatment rescued almost half of the entire dysregulated diurnal transcriptome patterns. A combination of E-box and glucocorticoid response elements is enriched in the rescued genes. This simple enhancer element combination is sufficient to drive rhythmic circadian reporter gene expression under non-rhythmic glucocorticoid exposure, revealing a permissive function for the hormones in glucocorticoid-dependent circadian transcription. Our work highlights metabolic pathways potentially contributing to morbidity in patients with glucocorticoid deficiency, even under glucocorticoid replacement therapy. Moreover, we provide mechanistic insight into the interaction between the circadian clock and glucocorticoids in the transcriptional regulation of metabolism. Overall design: RNA-Seq from total RNA of zebrafish larvae during (5 dpf) the diurnal cycle. Time-series mRNA profiles of untreated wild type (WT), rx3t25327/t25327 [rx3 strong] and rx3t25181/t25181 [rx3 weak] mutant larvae as well as dexamethasone treated WT and rx strong larvae were generated by deep sequencing.
Publication Title
Extensive Regulation of Diurnal Transcription and Metabolism by Glucocorticoids.
Sample Metadata Fields
No sample metadata fields
View Samples- Vitis riparia, Vitis hybrid cultivar
- 84 Downloadable Samples
- Affymetrix Vitis vinifera (Grape) Genome Array (vitisvinifera)
Description
Bud endodormancy induction response of two genotypes (Seyval a hybrid white wine grape and V. riparia, PI588259 a native north american species) was compared under long (15h) and short (13h) photoperiod. Three separate replicates (5 plants/replicate) were treated to generate paradormant (LD) and same aged endodormancy-induced (SD) buds for transcriptomic, proteomic and metabolomic analysis. Potted, spur-pruned two to six-year-old vines were removed from cold storage (Seyval 3-19-07; V. riparia 3/26/07) and grown under a LD (15 h) at 25/20 + 3C day/night temperatures (D/N). When vines reached 12-15 nodes (3-25-07) they were randomized into LD or SD treatments with 25/20 + 3C D/N in climate controlled greenhouses with automated photoperiod system (VRE Greenhouse Systems). Three replications (5 vines/replication) were harvested between 5/07-6/07 and then again in 5/08-6/08 for a total of six replications. All treatments are repeated at the same time every year and harvested at the same time of day each year to minimize biological noise. At 1, 3, 7, 14, 21, 28 and 42 days of LD and SD treatment, buds were harvested from nodes 3 to 12 of each separate replicate, immediately frozen in liquid nitrogen, and placed at -80C for future RNA, protein and metabolite extraction. These time points encompass early reversible phases as well as key time points during transition to irreversible endodormancy development. After photoperiod treatments and bud harvests, all pruned vines were returned to LD and monitored for bud endodormancy. The endodormant vines were identified after 28 days and moved to cold storage. The nondormant vines were allowed to grow again and induced into dormancy at a later date. Acknowledgement:This study was funded by NSF Grant DBI0604755 and funds from the South Dakota Agriculture Experiment Station. ****[PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor, Anne Fennell. The equivalent experiment is VV10 at PLEXdb.]
Publication Title
Differential floral development and gene expression in grapevines during long and short photoperiods suggests a role for floral genes in dormancy transitioning.
Sample Metadata Fields
Age, Specimen part
View Samples- Drosophila melanogaster
- 12 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
The formation of neuronal connections requires the precise guidance of developing axons towards their targets. In the Drosophila visual system, photoreceptor neurons (R cells) project from the eye into the brain. These cells are grouped into some 750 clusters comprised of eight photoreceptors or R-cells each. R cells fall into three classes, R1-R6, R7 and R8. Posterior R8 cells are the first to project axons into the brain. How these axons select a specific pathway is not known.
Publication Title
Robo-3--mediated repulsive interactions guide R8 axons during Drosophila visual system development.
Sample Metadata Fields
Specimen part
View Samples- Saccharomyces cerevisiae
- 6 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Studies of aging and longevity are revealing how diseases that shorten life can be controlled to improve the quality of life and lifespan itself. Two strategies under intense study to accomplish this goal are rapamycin treatment and calorie restriction. New strategies are being discovered including one that uses low-dose myriocin treatment. Myriocin inhibits the first enzyme in sphingolipid synthesis in all eukaryotes and we showed recently that low-dose myriocin treatment increases yeast lifespan at least in part by down-regulating the sphingolipid-controlled Pkh1/2-Sch9 (ortholog of mammalian S6 kinase) signaling pathway.
Publication Title
Reducing sphingolipid synthesis orchestrates global changes to extend yeast lifespan.
Sample Metadata Fields
No sample metadata fields
View Samples- Escherichia coli str. k-12 substr. mg1655
- 5 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
Carboxylic acids are an attractive biorenewable chemical. Enormous progress has been made in engineering microbes for production of these compounds though titers remain lower than desired.
Publication Title
Transcriptomic analysis of carboxylic acid challenge in Escherichia coli: beyond membrane damage.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 4 Downloadable Samples
- IlluminaHiSeq2000
Description
The goal of this study is to determine gene expression changes in the adult zebrafish spinal cord at 2 weeks after complete transection. Overall design: 2 samples were analyzed in duplicates: sham injured spinal cord and transected spinal cord at 2 weeks post-injury
Publication Title
Injury-induced ctgfa directs glial bridging and spinal cord regeneration in zebrafish.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Transcriptional reprogramming of CD11b+Esam(hi) dendritic cell identity and function by loss of Runx3.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples