We are investigating the transcriptional response of changes in RNA steady-state levels between normal and DM1.
RNA steady-state defects in myotonic dystrophy are linked to nuclear exclusion of SHARP.
Specimen part
View SamplesEnvironmental stress-induced transgenerational epigenetic effects have been observed in various model organisms and human. The capacity and mechanism of such phenomena, particularly in animals, are poorly understood. In C. elegans, siRNA mediates transgenerational gene silencing through the germline nuclear RNAi pathway. At the organismal level, this pathway plays a transgenerational role in maintaining the germline immortality when C. elegans is under a mild heat stress. However, the underlying molecular mechanism is unknown. In this study, we performed a 12-generation temperature-shift experiment (15°C->23°C->15°C) using the wild type (N2) and a mutant strain that lacks the germline-specific nuclear AGO protein HRDE-1/WAGO-9. We found that the temperature-sensitive mortal germline (Mrt) phenotype of the hrde-1 mutant is reversible, indicating a transgenerational cumulative but also reversible nature of the underlying molecular cause. By taking the whole-genome RNA and chromatin profiling approaches, we revealed an epigenetic role of HRDE-1 in repressing heat stress-induced transcriptional activation of over 280 genes, predominantly in or near LTR retrotransposons. Strikingly, for some of these elements, the heat stress-induced transcription becomes progressively activated in the hrde-1 mutant over several generations under heat stress. Furthermore, the effect of heat stress-induced transcription activation is heritable for at least two generations after the heat stress. Interestingly, the siRNA expression of these genes tend to be heat-inducible in the wild type animals, but not in the hrde-1 mutant, suggesting a role of siRNAs in repressing heat-inducible elements. Our study revealed a novel phenomenon of transgenerational feed-forward transcriptional activation, which is normally repressed in the wild type C. elegans by the germline nuclear RNAi pathway. It also provides a new paradigm to study epigenetic circuitry that connects the environment and gene regulation in the germline. Overall design: In this study, we performed a 12-generation temperature-shift experiment (15°C->23°C->15°C) using the wild type and hrde-1 mutant. mRNA-seq, Pol II ChIP-seq, H3K9me3 ChIP-seq, and small RNA-seq analyses were performed for all or some of the generations. The effects of temperature change in whole-genome mRNA expression, siRNA expression, gene transcription, and H3K9me3 were investigated at the multigenerational time scale in both the WT and hrde-1 mutant animals.
A transgenerational role of the germline nuclear RNAi pathway in repressing heat stress-induced transcriptional activation in C. elegans.
Subject
View SamplesDetailed analysis of genome-wide transcriptome profiling in rice root is reported here, following Cr-plant interaction. Such studies are important for the identification of genes responsible for tolerance, accumulation and defense response in plants with respect to Cr stress. Rice root metabolome analysis was also carried out to relate differential transcriptome data to biological processes affected by Cr (VI) stress in rice.
Transcriptomic and metabolomic shifts in rice roots in response to Cr (VI) stress.
Age, Specimen part, Treatment
View SamplesTraditional rice varieties found in India have many desirable characteristics. Amongst them, their differential responses to abiotic and biotic stresses are of great agricultural importance. Drought or osmotic stress is one of the major abiotic stresses afflicting crop plants in India. Indigenous varieties like Dagad deshi have been found to be drought resistant and, thereby, are being studied in great detail by plant breeders and biotechnologists alike. In this study, we have analyzed the transciptomes of two contrasting cultivars, i.e. Dagad deshi (tolerant) and IR20 (susceptible), under control and stress conditions to elucidate the differences in their responses to drought stress using Affymetrix microarray platform.
Reference genes for accurate gene expression analyses across different tissues, developmental stages and genotypes in rice for drought tolerance.
Specimen part, Time
View SamplesGene expression profiles were performed to compare the difference in sigmoid colon biopsies between from healthy control and patients with ulcerative colitis.
MicroRNAs are differentially expressed in ulcerative colitis and alter expression of macrophage inflammatory peptide-2 alpha.
No sample metadata fields
View SamplesA gene expression signature characterizes expression data from breast cancer samples of patients with pathological complete response (pCR) or residual disease (RD) following the neoadjuvant trial.
A gene expression signature that predicts the therapeutic response of the basal-like breast cancer to neoadjuvant chemotherapy.
Sex, Disease stage, Race
View SamplesInflammation has pleiotropic effects on carcinogenesis and tumor progression. Signaling through the adaptor protein MyD88 promotes carcinogenesis in several chemically induced cancer models. Interestingly, we observed a protective role for MyD88 in the development of AOM/DSS colitis-associated cancer. The inability of Myd88-/- mice to heal ulcers generated upon injury creates an inflammatory environment that increases the frequency of mutations and results in a dramatic increase in adenoma formation and cancer progression. Susceptibility to colitis development and enhanced polyp formation were also observed in Il18-/- mice upon AOM/DSS treatment, suggesting that the phenotype of MyD88 knockouts is in part due to their inability to signal through the IL-18 receptor. This study revealed a previously unknown level of complexity surrounding MyD88 activities downstream of different receptors that differentially impact tissue homeostasis and carcinogenesis.
MyD88-mediated signaling prevents development of adenocarcinomas of the colon: role of interleukin 18.
Specimen part, Disease, Disease stage
View SamplesMyeloid-derived cells comprising the tumor stroma represent a heterogeneous population of cells critical to the structure, function and growth of established cancers. We have recently found that engineering tumor-specific CD8+ T cells to secrete IL-12 (IL-12TD) can lead to striking improvements in T-cell activity against established melanomas in murine models. Surprisingly, IL-12-dependent enhancement of CD8+ T-cell anti-tumor function did not occur through direct ligation of receptors on lymphocytes or NK cells. Instead, IL-12 sensitized host bone marrow-derived tumor-stromal cells, partly through interferon-gamma, to indirectly enhance the effects of adoptively-transferred T cells. Direct presentation of antigen by tumor was not necessary, but MHC class I expression on endogenous cells was essential for IL-12 mediated anti-tumor enhancements. Upon successful treatment with IL-12TD cells, we observed the selective elimination of tumor-infiltrating CD11b+ F4/80+ macrophages, CD11b+/ClassII+/CD11c+ dendritic cells and CD11b+/Ly6C+/Ly6G- but not CD11b+/Ly6C+/Ly6G+ myeloid-derived suppressor cells within regressing lesions. These results are consistent with a model whereby IL-12 triggers the maturation of myeloid-derived cells into competent antigen cross-presenting cells. Licensed recognition of these antigens by effector T cells may in turn trigger the collapse of the tumor stroma and aid in the regression of large vascularized lesions.
IL-12 triggers a programmatic change in dysfunctional myeloid-derived cells within mouse tumors.
Specimen part, Disease, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Brain iron accumulation affects myelin-related molecular systems implicated in a rare neurogenetic disease family with neuropsychiatric features.
Sex, Age, Specimen part, Disease
View SamplesDifferential gene expression is assessed in substantia nigra and basal ganglia of neurodegenertion with brain iron accumulation cases (BIA) compared to matched normal controls (c).
Brain iron accumulation affects myelin-related molecular systems implicated in a rare neurogenetic disease family with neuropsychiatric features.
Sex, Age, Specimen part, Disease
View Samples