We study the effect of four QTN in RME1, IME1 & RSF1 that are causative for variation in sporulation efficiency. We investigate the relationship between genotype, gene expression and phenotype and whether the amount of gene expression variation explained by the sporulation QTN is predictive of the amount of phenotypic variation explained by them. Overall design: RNA-Seq analysis of 4 replicates each of 16 allele replacement panel strains containing all combinations of the four sporulation QTN after 2 hours in sporulation medium.
Single nucleotide variants in transcription factors associate more tightly with phenotype than with gene expression.
Subject
View SamplesParkinsons disease (PD) progresses relentlessly and affects five million people worldwide. Laboratory tests for PD are critically needed for developing treatments designed to slow or prevent progression of the disease. We performed a transcriptome-wide scan in 105 individuals to interrogate the molecular processes perturbed in cellular blood of patients with early-stage PD. The molecular marker here identified is strongly associated with risk of PD in 66 samples of the training set (third tertile cross-validated odds ratio of 5.7 {P for trend 0.005}). It is further validated in 39 independent test samples (third tertile odds ratio of 5.1 {P for trend 0.04}). The genes differentially expressed in patients with PD, or Alzheimers or progressive supranuclear palsy offer unique insights into disease-linked processes detectable in peripheral blood. Combining gene expression scans in blood and linked clinical data will facilitate the rapid characterization of candidate biomarkers as demonstrated here with respect to PD.
Molecular markers of early Parkinson's disease based on gene expression in blood.
No sample metadata fields
View SamplesRenal cell carcinoma (RCC) is among the ten most common malignancies. By far, the most common histology is clear cell (ccRCC). The Cancer Genome Atlas and other large scale sequencing studies of ccRCC have been integral to the current understanding of molecular events underlying RCC and its biology. However, these data sets have focused on primary RCC which often demonstrates indolent behavior. In contrast, metastatic disease is the major cause of mortality associated with ccRCC. However, data sets examining metastatic tumor are sparse. We therefore undertook an integrative analysis of gene expression and DNA methylome profiling of metastatic ccRCC in addition to primary RCC and normal kidney. Integrative analysis of the methylome and transcriptome identified over 30 RCC specific genes whose mRNA expression inversely correlated with promoter methylation including several known targets of hypoxia inducible factors (HIFs). Notably, genes encoding several metabolism-related proteins were identified as differentially regulated via methylation. Collectively, our data provide novel insight into biology of aggressive RCC. Furthermore, they demonstrate a clear role for epigenetics in the promotion of HIF signaling and invasive phenotypes in renal cancer.
Integrative Epigenetic and Gene Expression Analysis of Renal Tumor Progression to Metastasis.
Specimen part
View SamplesUnderstanding gene expression changes during transformation from normal tissue to primary RCC and then to metastasis is important. Such analysis is pivotal for undertanding biology in renal cancer and also to unearth novel gene targets.
Integrative Epigenetic and Gene Expression Analysis of Renal Tumor Progression to Metastasis.
Specimen part
View SamplesAnalysis of gene expressions in mouse splenic dendritic cells (DCs). DCs were purified into two subsets, CD8-positive and -negative ones. DCs were expanded in vivo by injecting Flt3L-producing tumors into the backs of C57BL/6 mice.
A new triggering receptor expressed on myeloid cells (Trem) family member, Trem-like 4, binds to dead cells and is a DNAX activation protein 12-linked marker for subsets of mouse macrophages and dendritic cells.
No sample metadata fields
View SamplesWe enriched for prostate cancer cells by the selection system used in human iPS purification. Gene expression signature-based chemical prediction enabled us to identify candidate drugs for reverting the EOS (early transposon promoter, OCT4 and SOX2 enhancer) signature with chemoresistance into a chemosensitive phenotype.
Identification of drug candidate against prostate cancer from the aspect of somatic cell reprogramming.
Specimen part, Cell line, Treatment
View SamplesSide population (SP) cells are identified based on their capacity to efflux of the fluorescent dye Hoechst 33342, and are enriched for hematopoietic stem cells (HSCs) in mammalian bone marrow. We recently demonstrated that SP cells were present in the teleost kidney, the main hematopoietic organ in teleosts, and were enriched for HSCs. In this analysis, to identify the regulated genes in teleost HSCs, gene expression analysis of zebrafish kidney SP cells were performed using the GeneChip Zebrafish Genome Array.
Comparative gene expression analysis of zebrafish and mammals identifies common regulators in hematopoietic stem cells.
No sample metadata fields
View SamplesThis study aimed to clarify the role of PRMT5 in the hematopoietic stem cell (HSC) compartment, and elucidate the functional relevance of PRMT5-mediated splicing in HSCs. We confirm the cell intrinsic requirement for PRMT5 in HSC maintenance, and present evidence suggesting that PRMT5 deficiency perturbs HSC proteostasis. Notably, we also uncover a critical role for PRMT5 in maintaining HSC genomic integrity by modulating splicing of genes involved in DNA repair; loss of which leads to unresolved DNA damage, p53 activation and rapid HSC exhaustion. Overall, these findings establish PRMT5-mediated splicing as a major determinant of HSC fate, and highlight the need to maintain an adequate level of PRMT5 activity in HSCs. Overall design: Hematopoietic stem cells (HSCs; Lineage-Sca-1+CD48-CD150+), isolated from Prmt5fl/fl or Prmt5?/? littermate- and gender-matched mice 7 days post-induction, were subjected to RNA-seq. HSCs for each independent sample were obtained from bone marrow cells pooled from two mice. Three independent samples were obtained for each group.
PRMT5 Modulates Splicing for Genome Integrity and Preserves Proteostasis of Hematopoietic Stem Cells.
Specimen part, Cell line, Subject
View SamplesAppropriate regulation of hematopoietic stem cell (HSC) self-renewal is critical for the maintenance of life long hematopoiesis. However, long-term repeated cell divisions induce the accumulation of DNA damage, especially at telomere, significantly compromises HSC function. Therefore, shelterin elements Pot1a is required to prevent DNA damage response at telomeres in order to maintain their function.
The telomere binding protein Pot1 maintains haematopoietic stem cell activity with age.
Sex, Specimen part
View SamplesPurpose: The goals of this study are to elucidate the influence of integrin ß3 signaling on STAT1-dependnet gene expression in IFN?-treated HSCs. Methods: Wild type (WT) HSCs were cultured with or without IFN? and/or VN in the presence of stem cell factor (SCF) plus thrombopoietin (TPO). Subsequently, cultured HSC fraction (CD48- c-kit+ Sca-1+ Lineage-) were sorted, followed by mRNA sequence using Ion Proton (n>4). Moreover, to extract genes whose expression were changed via STAT1 in the presence of IFN?, mRNA profiles of STAT1-/- HSCs treated with or without IFN? were also generated by the same way. The sequence reads that passed quality filters were analyzed by CLC genomic workbench. Results: Using an optimized data analysis workflow, we mapped about 30 million sequence reads per sample to the mouse genome (build mm10) with CLC genomic workbench. Indeed, hierarchical clustering analysis showed that IFN?-treated STAT1-/- HSCs was categorized to the group including Wt HSCs cultured in the absence of IFN? rather than HSCs treated with IFN?. Furthermore, gene set enrichment analysis (GSEA) showed that STAT1-dependent upregulated gene sets were significantly enriched within genes whose expression was enhanced in HSCs treated with VN and IFN?. In contrast, integrin ß3 signaling in the absence of IFN? appears to not influence the expression of IFN?/STAT1-dependent genes, as evidenced by the observation that VN treatment was statistically and significantly independent of the enrichment of gene sets that were both up-regulated by STAT1 Conclusions: Our study represents that STAT1 plays a central role in IFN?-mediated HSC responses and integrin ß3 signaling in HSCs promotes STAT1-dependent gene expression in the presence of IFN?. Overall design: After HSCs derived from wild type (WT) and STAT1-/- mice were treated with IFNg and/or vitronectin for 5 days, mRNA profiles were generated by deep sequencing using Ion Proton system (n>4).
Integrin αvβ3 enhances the suppressive effect of interferon-γ on hematopoietic stem cells.
Specimen part, Cell line, Subject
View Samples