Precise regulation of stem cell self-renewal and differentiation properties is essential for tissue homeostasis. Using the adult Drosophila intestine to study molecular mechanisms controlling stem cell properties, we identify the gene split-ends (spen) in a genetic screen as a novel regulator of intestinal stem cell fate. Spen family genes encode conserved RNA recognition motif-containing proteins that are reported to have roles in RNA splicing and transcriptional regulation. We demonstrate that spen loss of function in intestinal stem cells results in an abnormal increase in the number of stem cell-like cells and that Spen acts to control early commitment events of the stem cells. Using two-color cell sorting of stem cells and their daughters, we characterize spen-dependent changes in RNA abundance and exon usage, and find potential key regulators downstream of spen. Our work identifies spen as an important regulator of adult stem cells in the Drosophila intestine, provides new insight to Spen-family protein functions, and may also shed light on Spen's mode of action in other developmental contexts. Overall design: Three biological replicates were sequenced per each 4 conditions
Spen limits intestinal stem cell self-renewal.
Sex, Age, Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Nuclear mTOR acts as a transcriptional integrator of the androgen signaling pathway in prostate cancer.
Cell line, Treatment
View SamplesWhether the nuclear fraction of mTOR plays a role in prostate cancer (PCa) and can participate in direct transcriptional crosstalk with the androgen receptor (AR) is as yet unknown. The intersection of gene expression, DNA binding-events, and metabolic studies uncovered the existence of a nuclear mTOR-AR transcriptional axis dictating the metabolic rewiring and nutrient usage of PCa cells. In human clinical specimens, nuclear localization of mTOR was significantly associated with metastasis and castration-resistant PCa (CRPC), correlating with a sustained metabolic gene program governed by mTOR in that context. This study thus uncovers an unexpected function of mTOR and underscores a paradigm shift from AR to mTOR as being the master transcriptional regulator of cell metabolism during PCa progression.
Nuclear mTOR acts as a transcriptional integrator of the androgen signaling pathway in prostate cancer.
Cell line
View SamplesHonokiol (HNK), one of the main medicinal components in Magnolia officinalis, possesses antimicrobial activity against a variety of pathogenic bacteria and fungi.S. cerevisiae is a model eukaryote used for investigating the cellular and molecular mechanisms of anti-fungal drugs.
Transcriptomic analysis of Saccharomyces cerevisiae upon honokiol treatment.
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View SamplesBackgroud:Epigenetic modifications (especially altered DNA methylation) resulting in altered gene expression may be one reason for development failure or the abnormality of the cloned animals, but the underlying mechanism of the abnormal phenotype in the cloned piglets remains unrevealed. Some cloned piglets in our study showed abnormal phenotypes such as big tongue (longer and thicker), limp, and exomphalos, which is similar to the human BWS syndrome. Here we conducted DNA methylation (DNAm) immunoprecipitation binding high throughput sequencing (MeDIP-seq) and RNA sequencing (RNA-seq) of muscle tissues of cloned piglets to investigate the relationship of abnormal DNAm with gene dysregulation and the unusual phenotypes in cloned piglets. Results:Analysis of the methylomes revealed that abnormal cloned piglets suffered more hypomethylated differentially methylated regions (DMRs) than hypermethylated DMRs compared to the normal cloned piglets. The DNAm level in the CpG Island was higher in the abnormal cloned piglets. Some repetitive elements, such as SINE/tRNA-Glu Satellite/centr also showed significant differences. Besides we detected 1,711 differentially expressed genes (DEGs) between the two groups, of which 243 genes also changed methylation level in the abnormal cloned piglets. The altered DNA methylation mainly affected the low and silent expression genes. We also found some interesting pathways and genes, such as MAPK signalling pathway, hypertrophic cardiomyopathy pathway, TPM3 gene and the imprinted gene PLAGL1, which may played important roles in the abnormal phenotype development. Conclusions;The abnormal cloned piglets showed substantial change both in the DNAm and the gene expression levels. Our data may provide new insights into understanding the molecular mechanisms of the reprogramming of genetic information in cloned animals. Overall design: We dissected the biceps femoris muscle from the abnormal cloned piglets and the normal cloned piglets, and analyzed the difference of MeDIP-seq and RNA-seq between the two groups. This represents the RNA-Seq study only
Transcriptome analysis reveals long intergenic non-coding RNAs involved in skeletal muscle growth and development in pig.
Specimen part, Subject
View SamplesSomatic cell nuclear transfer has brought considerable chances to breed excellent breeds and protect endanger animals, while also produced numerous fail embryos and abnormal individuals due to inefficient epigenetic modification at the same time. To understand some mechanisms of abnormal piglets with phenotypes such as macroglossia, standing and walking disabilities in our study and find some differences between abnormal piglets and conventionally bred normal piglets, DNA methylation profile and genome-wide gene expression were conducted in two groups, using methylated DNA immunoprecipitation binding highthroughput sequencing (MeDIP-Seq) and RNA sequencing(RNA-Seq). We generated and provided a genome-wide DNA methylation and gene expression profile for abnormal cloned and conventionally bred piglets. We detected a total of 1493 genes differentially expressed in two groups and 382 of these genes also differentially methylated in two groups. Analysis of relationship between DNA methylation and gene expression revealed that DNA methylation levels had significantly negative and monotonic correlation with gene expression levels in particular regions of genes while no obvious monotonic correlation in other regions. Besides, we found some interesting genes and pathways such as MYH7 and mTOR signalling pathway that may played essential role in muscle growth and development. Briefly, these results provide reliable data for future epigenetic studies and may help to uncover the mechanism of failure clones via SCNT. Overall design: We dissected the leg muscle from the cloned piglets and the conventionally bred piglets, and analyzed the difference of MeDIP-seq and RNA-seq between the two groups. As for data of abnormal cloned piglets, we downloaded it from GEO under Super-Series accession No. GSE51477, including SubSeries accession No.GSE51282 for RNA-seq data (No. GSM1241829 for abnormal cloned group) and SubSeries accession No. GSE51476 for MeDIP-seq data (No. GSM1246252 for abnormal cloned group).
Transcriptome analysis reveals long intergenic non-coding RNAs involved in skeletal muscle growth and development in pig.
Specimen part, Subject
View SamplesThis series contain time course microarray data from MCF10A-Myc cells treated with either ethanol or Dexamethasone for 30 min, 2 hr, 4 hr, and 24 hr. This series contains three biological replicates that were analyzed as independent replicate experiments (data were normalized within each replicate experiment, not across all samples).
Glucocorticoid receptor activation signals through forkhead transcription factor 3a in breast cancer cells.
Age
View SamplesPollen germination, along with pollen tube growth, is an essential process for the reproduction of flowering plants. The germinating pollen with tip-growth characteristics provides an ideal model system for the study of cell growth and morphogenesis. As an essential step towards a detailed understanding of this important process, the objective of this study was to comprehensively analyze the transcriptome changes during pollen germination and pollen tube growth. Using Affymetrix Arabidopsis ATH1 Genome Arrays, this study is the first to show the changes in the transcriptome from desiccated mature pollen grains to hydrated pollen grains and then to pollen tubes of Arabidopsis thaliana. The number of expressed genes, either for total expressed genes or for specifically expressed genes, increased significantly from desiccated mature pollen to hydrated pollen and again to growing pollen tubes, which is consistent with the finding that pollen germination and tube growth was significantly inhibited in vitro by a transcriptional inhibitor. The results of GO analyses showed that expression of genes related to cell rescue, transcription, signal transduction and cellular transport were significantly changed, especially for up-regulation, during pollen germination and tube growth, respectively. In particular, genes of the CaM/CML, CHX and Hsp families showed the most significant changes during pollen germination and tube growth. These results demonstrate that the overall transcription of genes, both in the number of expressed genes and in the levels of transcription, was increased. Furthermore, the appearance of many novel transcripts during pollen germination as well as tube growth indicates that these newly expressed genes may function in this complex process.
Transcriptome analyses show changes in gene expression to accompany pollen germination and tube growth in Arabidopsis.
Age, Specimen part
View SamplesBackground: Alternative polyadenylation (APA) is emerging as a widespread mechanism of gene regulation. The usage of APA sites allows a single gene to encode multiple mRNA transcripts with different 3''-untranslated region (3''UTR) lengths. Many disease processes reflect the importance of the regulation of APA site switching. The objective of this study was to explore the profiling of tandem APA sites in nasal polyps compared with nasal uncinate process mucosa. Methods: Sequencing of APA sites (SAPAS) based on second-generation sequencing technology was undertaken to investigate the use of tandem APA sites and identify gene expression patterns in samples from the nasal polyps and nasal uncinate process mucosa of two patients with chronic rhinosinusitis with nasal polyps. The findings of the SAPAS analysis were validated via quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Results: First, the results showed a switching of 3''UTR lengths in nasal polyps compared with nasal uncinate process mucosa. From the two patients, 105 overlapping genes in the nasal polyps were switched to distal poly(A) sites, and 90 such genes were switched to proximal poly(A) sites. Several Gene Ontology terms were enriched in the list of genes with switched APA sites, including transcription regulation, cell cycle, apoptosis, and metabolism. Second, we detected genes that showed differential expression with at least a 3-fold difference between nasal polyp tissue and nasal uncinate process mucosa. Between the two sample types, 627 genes exhibited differential expression. The qRT-PCR results confirmed our SAPAS results. Conclusion: APA site-switching events of 3''UTRs are prevalent in nasal polyp tissue, and the regulation of gene expression mediated by APA may play an important role in the formation and persistence of nasal polyps. Our results may provide new insights into the possible pathophysiologic processes involved in nasal polyps. Overall design: Investigate the use of tandem APA sites of 3''ends of mRNAs using second-generation sequencing technology.
A global analysis of tandem 3'UTRs in eosinophilic chronic rhinosinusitis with nasal polyps.
Sex, Age, Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Predicting Drug Response in Human Prostate Cancer from Preclinical Analysis of In Vivo Mouse Models.
Specimen part, Disease, Disease stage, Treatment
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