Fumarate hydratase (FH) mutation causes hereditary type 2 papillary renal cell carcinoma (HLRCC, Hereditary Leiomyomatosis and Renal Cell Cancer (MM ID # 605839)). The main effect of FH mutation is fumarate accumulation. The current paradigm posits that the main consequence of fumarate accumulation is HIF-a stabilization. Paradoxically, FH mutation differs from other HIF-a stabilizing mutations, such as VHL and SDH mutations, in its associated tumor types. We identified that fumarate can directly up-regulate antioxidant response element (ARE)-controlled genes. We demonstrated that AKR1B10 is an ARE-controlled gene and is up-regulated upon FH knockdown as well as in FH-null cell lines. AKR1B10 overexpression is also a prominent feature in both hereditary and sporadic PRCC2. This phenotype better explains the similarities between hereditary and sporadic PRCC2.
An antioxidant response phenotype shared between hereditary and sporadic type 2 papillary renal cell carcinoma.
Disease, Disease stage
View SamplesA soybean ortholog of the Arabidopsis MADS-domain transcription factor (called GmAGL15) enhanced somatic embryogenesis from immature cotyledon explants of soybean when expressed via the 35S promoter compared to non transgenic tissue (cultivar Jack). To better understand how this occurs an expression microarray experiment was performed.
Alterations in the transcriptome of soybean in response to enhanced somatic embryogenesis promoted by orthologs of Agamous-like15 and Agamous-like18.
Specimen part, Time
View SamplesSle1c is a sublocus of the NZM2410-derived Sle1 major susceptibility locus. We have previously shown that Sle1c contributes to lupus pathogenesis by conferring CD4+ T cell-intrinsic hyperactivation and increased susceptibility to chronic graft-versus-host disease (cGVHD) that mapped to the centromeric portion of the locus. In this study, we have refined the centromeric sublocus to a 675Kb interval, termed Sle1c2. Recombinant congenic strains expressing Sle1c2 exhibited a T cell-intrinsic CD4+ T cell hyperactivation and cGVHD susceptibility, similar to mice with the parental Sle1c.
Murine lupus susceptibility locus Sle1c2 mediates CD4+ T cell activation and maps to estrogen-related receptor γ.
Sex, Age, Specimen part
View SamplesA mutant previously isolated from a screen of EMS-mutagenized Arabidopsis lines, per1, showed normal root hair development under control conditions but displayed an inhibited root hair elongation phenotype upon Pi deficiency. Additionally, the per1 mutant exhibited a pleiotropic phenotype under control conditions, resembling Pi-deficient plants in several aspects. Under Pi deficiency, the accumulation of Pi and iron was increased in the mutant when compared to the wild-type. Inhibition of root hair elongation upon growth on low Pi media was reverted by treatment with the Pi analog phosphite, suggesting that the mutant phenotype is not the result of a defect in Pi sensing. Reciprocal grafting experiments revealed that the mutant rootstock is sufficient to cause the phenotype. Transcriptional profiling of per1 and wild-type plants subjected to short-term Pi starvation revealed genes that may be important for the signaling of Pi deficiency. We conclude that UBP14 function is crucial for adapting root development to the prevailing local availability of phosphate.
Ubiquitin-specific protease 14 (UBP14) is involved in root responses to phosphate deficiency in Arabidopsis.
Specimen part
View SamplesThe lack of suitable animal models reflecting chronically relapsing inflammation and tissue remodeling have hindered fibrosis research in inflammatory bowel diseases (IBD). This study investigated changes in connective tissue in a chronic murine model using different cycles of dextran sodium sulphate (DSS) to mimic the relapsing nature of the disease.
Unique gene expression and MR T2 relaxometry patterns define chronic murine dextran sodium sulphate colitis as a model for connective tissue changes in human Crohn's disease.
Sex, Age, Specimen part
View SamplesMuscle satellite cells are a self-renewing pool of stem cells that give rise to daughter myogenic precursor cells in adult skeletal muscle. Published and preliminary data indicated that MyoD and p53 genes are involved in satellite cell differentiation. We would like to know what downstream genes of both transcription factors are affected in satellite cell-derived myoblasts (MyoD-/-, p53 -/-).
MyoD induces myogenic differentiation through cooperation of its NH2- and COOH-terminal regions.
No sample metadata fields
View SamplesThe Affymetrix Human Genome U133 Plus 2.0 Array was used to examine the Genome wide transcriptional changes which follow the treatment of AML xenografts with either PBS control or combination of decitabine (DAC) and cytarabine (Ara-C). Animals were treated with PBS, DAC alone, Ara-C alone, DAC and Ara-C combined (D+A), DAC followed by Ara-C (D/A) or Ara-C followed by DAC (A/D).
Sequential treatment with cytarabine and decitabine has an increased anti-leukemia effect compared to cytarabine alone in xenograft models of childhood acute myeloid leukemia.
Specimen part, Disease
View SamplesSkeletal muscle senescence influences whole organism aging, yet little is known on the relay of pro-longevity signals from muscles to other tissues. We performed an RNAi screen in Drosophila for muscle-released cytokines (?myokines?) regulating lifespan and identified Myoglianin, the homolog of human Myostatin. Myoglianin is induced in skeletal muscles by the transcription factor Mnt and together they constitute an inter-organ signaling module that regulates lifespan, age-related muscle dysfunction, and protein synthesis across aging tissues. Both Mnt and Myoglianin activate already in young age the protective decline in protein synthesis that is typical of old age, while knock-down of Myoglianin impairs this process. Mechanistically, Mnt decreases the expression of nucleolar components in muscles while also decreasing nucleolar size in distant tissues via Myostatin/p38 MAPK signaling. Our results highlight a myokine-dependent inter-organ longevity pathway that coordinates nucleolar function and protein synthesis across aging tissues.
Intertissue control of the nucleolus via a myokine-dependent longevity pathway.
Sex, Specimen part, Treatment
View SamplesIdentifying putative transcription factor target genes by combining CRISPR/Cas9-based transcriptional activation with RNAseq in Drosophila S2R+ cells. This study focuses on the transcription factors Twist and Snail, singly and together. Overall design: RNA from Drosophila cells following CRISPR/Cas9-based activation of Twist, Snail, or Twist and Snail together, compared with non-targeting sgRNA. Two biological replicates for each experiment
In Vivo Transcriptional Activation Using CRISPR/Cas9 in Drosophila.
Specimen part, Treatment, Subject
View SamplesTo understand the function of gene CG7358 in Drosophila melanogaster, including indentification of those genes whose expression levels or alternative splicing are affected by CG7358. Overall design: 6 samples are analyzed, including 3 replicates for CG7358 mutant and the other 3 for wild type fly
Xio is a component of the <i>Drosophila</i> sex determination pathway and RNA <i>N</i><sup>6</sup>-methyladenosine methyltransferase complex.
Specimen part, Cell line, Subject
View Samples