Abstract: During Drosophila oogenesis, germline stem cell (GSC) identity is maintained largely by preventing the expression of factors that promote differentiation. This is accomplished via the activity of several genes acting either in the GSC or its niche. The translational repressors, Nanos and Pumilio, act in GSCs to prevent differentiation, likely by inhibiting translation of early differentiation factors, while niche signals prevent differentiation by silencing transcription of the differentiation factor Bam. We have found that the DNA-associated protein Stonewall (Stwl) is also required for GSC maintenance. stwl is required cell-autonomously; clones of stwl- germ cells were lost by differentiation, and ectopic Stwl caused an expansion of GSCs. stwl mutants acted as Suppressors of Variegation, indicating stwl normally acts in chromatin-dependent gene repression. In contrast to several previously described GSC maintenance factors, Stwl likely functions epigenetically to prevent GSC differentiation. Stwl-dependent transcriptional repression does not target bam, but rather Stwl represses the expression of many genes, including those that may be targeted by Nanos/Pumilio translational inhibition.
Stonewalling Drosophila stem cell differentiation by epigenetic controls.
No sample metadata fields
View SamplesRecurrent somatic hotspot mutations of DICER1 appear to be clustered around each of four critical metal binding residues in the RNase IIIB domain of DICER1. This domain is responsible for cleavage of the 3 end of the 5p-miRNA strand of a pre-mRNA hairpin. To investigate the effects of these cancer-associated hotspot mutations we engineered mouse Dicer1-deficient ES cells to express wild-type and an allelic series of the mutant human DICER1 variants. Global miRNA and mRNA profiles from cells carrying the metal binding site mutations were compared to each other and wild-type human DICER1. The miRNA and mRNA profiles generated through the expression of the hotspot mutations were virtually identical, and the DICER1 hotspot mutation carrying cells were distinct from both wild-type and Dicer1-deficient cells. Further, miRNA profiles showed mutant DICER1 results in a dramatic loss in processing of mature 5p-miRNA strands but were still able to create 3p-strand miRNAs. Messenger-RNA profile changes were consistent with the loss of 5p-strand miRNAs and showed enriched expression for predicted targets of the lost 5p derived miRNAs. We therefore conclude that cancer-associated somatic hotspot mutations of DICER1, affecting any one of four metal binding residues in the RNase IIIB domain, are functionally equivalent with respect to miRNA-processing and are hypomorphic alleles, yielding a global loss in processing of mature 5p-strand miRNA. We further propose that this resulting 3p-strand bias in mature miRNA expression likely underpins the oncogenic potential of these hotspot mutations.
Cancer-associated somatic DICER1 hotspot mutations cause defective miRNA processing and reverse-strand expression bias to predominantly mature 3p strands through loss of 5p strand cleavage.
Specimen part
View SamplesA distinct highly invasive subpopulation was identified in breast cancer cell lines. The molecular characteristics of these cells was investigated, revealing a set of genes whose high expression confers the ability to invade.
ΔNp63α Promotes Breast Cancer Cell Motility through the Selective Activation of Components of the Epithelial-to-Mesenchymal Transition Program.
Cell line
View SamplesWe conducted a time series of transcriptomics measurements during normal ageing in C. elegans in two non-reproductive strains (fem and gem) during normal ageing (days 1 to 10 of adulthood) and used this together with a multi-omics modelling pipeline to explore the changes that take place due to ageing. Overall design: Two strains and several time points with three replicates per strain and time point.
Multi-Omics and Genome-Scale Modeling Reveal a Metabolic Shift During <i>C. elegans</i> Aging.
Age, Specimen part, Subject
View SamplesWe assessed the gene expression profile of purified CD205+CD8+ Dendritic Cells isolated from murine spleens.
NOD2 modulates immune tolerance via the GM-CSF-dependent generation of CD103<sup>+</sup> dendritic cells.
Sex, Age, Specimen part
View SamplesPHF8 exerts distinct functions in different types of cancer. However, the mechanisms underlying its specific functions in each case remain obscure. To establish whether overexpression of PHF8 regulates the TGF-ß induced the epithelial-mesenchymal transition (EMT), we treated MCF10A-Mock (control) and MCF10A-PHF8wt (overexpressing wild-type PHF8) cells with TGF-ß1 for 0, 24, 48 and 72 hours and performed RNA-seq in biological duplicates. Our data indicated that EMT gene signatures were significantly enriched in MCF10A-PHF8 cells with TGF-ß1 treatment at all time points, strongly indicating that PHF8 overexpression induces a sustained EMT signaling program. Overall design: mRNA profiles of MCF10A-Mock (control) and MCF10A-PHF8 with TGF-ß1 treatment for 0, 24, 48 and 72 hours were generated by RNA-seq, in duplicate, using HiSeq2500 instrument.
Histone demethylase PHF8 promotes epithelial to mesenchymal transition and breast tumorigenesis.
No sample metadata fields
View SamplesWe sorted Eomes-negative NK cells (CD3- CD56+ CXCR6- CD16-) and Eomes-positive NK cells (CD3- CD56+ CXCR6+) from total leukocytes isolated from the perfusion fluid of five healthy human livers destined for transplantation. Total RNA was extracted from sorted cells, cDNA generated and RNASeq performed. Overall design: Examination of mRNA levels in paired Eomes-negative/Eomes-positive NK cells from the same donor.
Eomeshi NK Cells in Human Liver Are Long-Lived and Do Not Recirculate but Can Be Replenished from the Circulation.
Specimen part, Subject
View SamplesIt has long been appreciated that striped pair-rule transcription factor expression is necessary for convergent extension in the early Drosophila embryo, although the mechanisms that link these transcriptional regulators to planar polarity in this tissue have long been elusive. The goal of this study was to determine the transcriptional tragets of the pair-rule transcription factors Eve and Runt in Drosophila blastoderm embryos. We compared the transcriptional profiles of late blastoderm embryos injected with either water or dsRNAs against both eve and runt to identify differentially expressed genes that may directly contribute to the establishment of planar polarity during Drosophila convergent extension. Overall design: Comparing the mRNA profiles from late blastoderm Drosophila embryos injected with either water (Water) or eve+runt dsRNAs (Eve), in triplicate, using Illumina HiSeq.
A positional Toll receptor code directs convergent extension in Drosophila.
Subject
View SamplesGene expression profiles from 280 formalin-fixed and paraffin embedded normal and tumor samples of four cancer types
Regulatory T-cell Genes Drive Altered Immune Microenvironment in Adult Solid Cancers and Allow for Immune Contextual Patient Subtyping.
Sex, Age, Specimen part
View SamplesMM1S cells have been cultured under normoxic and hypoxic conditions, and gene expression profiling has been performed using the Affymetrix Human Genome U133 Plus 2.0 array.
Metabolic signature identifies novel targets for drug resistance in multiple myeloma.
Cell line
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