The goal of the study was to characterize the molecular signatures of CD8 T cell subpopulations sorted from HIV+ lymph nodes and HIV- tonsils. We compared the transcriptome profiles of follicular and non -foliccular CD8 T cells (sorted based on the surface expression fo CCR7 and CXCR5, chemokine receptors that govern the intratissue trafficking of T cells). This is the first study addressing this question. We found several genes differentially expressed in these two CD8 T cell populations. Our pathway analysis revealed that several pathways related to costimulation/activation as well as to beta-catenin pathway were differentially expressed in these two CD8 t cell populations too. Overall design: CD8 T cell populations were sorted and whole transcriptome analysis was performed using an Illumina machine
Follicular CD8 T cells accumulate in HIV infection and can kill infected cells in vitro via bispecific antibodies.
No sample metadata fields
View SamplesIn germ cells, Piwi proteins interact with a specific class of small non-coding RNAs, piwi-interacting RNAs (piRNAs). Together, these form a pathway that represses transposable elements, thus safeguarding germ cell genomes. While basic models describe the operation of piRNA pathways, neither the protein compositions of Piwi complexes, the critical protein-protein interactions that drive small RNA production and target recognition, or the precise molecular consequences of conserved localization to germline structures, call nuage, is well understood. We purified the three murine Piwi family proteins, Mili, Miwi, and Miwi2, from mouse germ cells and characterized their interacting protein partners. Piwi proteins were found in complex with Prmt5/Wdr77, an enzyme that di-methylates arginine residues. By immunoprecipitation with specific antibodies and by mass spectrometry, we found that Piwi proteins are arginine methylated at conserved positions in their amino termini. These modifications are essential to direct complex formation with specific Tudor-domain proteins, whose interactions with Piwis can be required for localization of RNP complexes in cytoplasmic nuage, proper piRNA expression, and transposon silencing. Considered together, our findings indicate that arginine methylation drives the assembly of multi-protein machines whose integrity and specific sub-cellular localization is necessary for efficient function of the piRNA pathway. Keywords: gene regulation study Overall design: Total small RNA in embryonic and post-birth mouse testes of tdrd1 and tdrd6 mutants
RNF17 blocks promiscuous activity of PIWI proteins in mouse testes.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A role for microRNAs in the Drosophila circadian clock.
Specimen part, Time
View SamplesPiwi proteins and their associated small RNAs are essential for fertility in animals. This is due, in part, to their roles in guarding germ cell genomes against the activity of mobile genetic elements. piRNA populations direct Piwi proteins to silence transposon targets and as such form a molecular code that discriminates transposons from endogenous genes. Information ultimately carried by piRNAs is encoded within genomic loci, termed piRNA clusters. These give rise to long, single-stranded, primary transcripts that are processed into piRNAs. Despite the biological importance of this pathway, neither the characteristics that define a locus as a source of piRNAs nor the mechanisms that catalyze primary piRNA biogenesis are well understood. We searched an EMS-mutant collection annotated for fertility phenotypes for genes involved in the piRNA pathway. Twenty-seven homozygous-sterile strains showed transposon-silencing defects. One of these, which strongly impacted primary piRNA biogenesis, harbored a causal mutation in CG5508, a member of the Drosophila glycerol-3-phosphate O-acetyltransferase (GPAT) family. These enzymes catalyze the first acylation step on the path to the production of phosphatidic acid (PA). Though this pointed strongly to a function for phospholipid signaling in the piRNA pathway, a mutant form of CG5508, which lacks the GPAT active site, still functions in piRNA biogenesis. We have named this new biogenesis factor Minotaur. Overall design: Examination of transcriptom profile in heterozygous and homozygous CG5508 mutant ovaries
Minotaur is critical for primary piRNA biogenesis.
Specimen part, Cell line, Subject
View SamplesPiwi proteins and their associated small RNAs are essential for fertility in animals. This is due, in part, to their roles in guarding germ cell genomes against the activity of mobile genetic elements. piRNA populations direct Piwi proteins to silence transposon targets and as such form a molecular code that discriminates transposons from endogenous genes. Information ultimately carried by piRNAs is encoded within genomic loci, termed piRNA clusters. These give rise to long, single-stranded, primary transcripts that are processed into piRNAs. Despite the biological importance of this pathway, neither the characteristics that define a locus as a source of piRNAs nor the mechanisms that catalyze primary piRNA biogenesis are well understood. We searched an EMS-mutant collection annotated for fertility phenotypes for genes involved in the piRNA pathway. Twenty-seven homozygous-sterile strains showed transposon-silencing defects. One of these, which strongly impacted primary piRNA biogenesis, harbored a causal mutation in CG5508, a member of the Drosophila glycerol-3-phosphate O-acetyltransferase (GPAT) family. These enzymes catalyze the first acylation step on the path to the production of phosphatidic acid (PA). Though this pointed strongly to a function for phospholipid signaling in the piRNA pathway, a mutant form of CG5508, which lacks the GPAT active site, still functions in piRNA biogenesis. We have named this new biogenesis factor Minotaur. Overall design: Examination of small RNA profile in heterozygous and homozygous CG5508 mutant ovaries
Minotaur is critical for primary piRNA biogenesis.
Specimen part, Cell line, Subject
View SamplesSnf1 and TORC1 are two global regulators that sense the nutrient availability and regulate the cell growth in yeast Saccharomyces cerevisiae. Here we undertook a systems biology approach to study the effect of deletion of these genes and investigate the interaction between Snf1 and TORC1 in regulation of gene expression and cell metabolism.
Mapping the interaction of Snf1 with TORC1 in Saccharomyces cerevisiae.
No sample metadata fields
View SamplesAltered expression of microRNAs (miRNAs), an abundant class of small non-protein-coding RNAs that mostly function as negative regulators of protein-coding gene expression, is common in cancer. Here we analyze the regulation of miRNA expression in response to estrogen, a steroid hormone that is involved in the development and progression of breast carcinomas and that is acting via the estrogen receptors (ER) transcription factors. We set out to thoroughly describe miRNA expression, by using miRNA microarrays and real time RTPCR experiments, in various breast tumor cell lines in which estrogen signaling has been induced by 17-estradiol (E2). We show that the expression of a broad set of miRNAs decreases following E2 treatment in an ER-dependent manner. We further show that enforced expression of several of the repressed miRNAs reduces E2-dependent cell growth, thus linking expression of specific miRNAs with estrogen-dependent cellular response. In addition, a transcriptome analysis revealed that the E2-repressed miR-26a and miR-181a regulate many genes associated with cell growth and proliferation, including the progesterone receptor gene, a key actor in estrogen signaling. Strikingly, miRNA expression is also regulated in breast cancers of women who had received antiestrogen neoadjuvant therapy thereby showing an estrogen-dependent in vivo regulation of miRNA expression. Overall, our data indicates that the extensive alterations in miRNA regulation upon estrogen signalling pathway plays a key role in estrogen-dependent functions and highlights the utility of considering miRNA expression in the understanding of antiestrogen resistance of breast cancer.
Widespread estrogen-dependent repression of micrornas involved in breast tumor cell growth.
Cell line
View SamplesTo identify differences in gene expression between peptidylprolyl isomerase F (cyclophilin D; Ppif)-null hearts and WT control hearts.
Cyclophilin D controls mitochondrial pore-dependent Ca(2+) exchange, metabolic flexibility, and propensity for heart failure in mice.
Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Blood coagulation protein fibrinogen promotes autoimmunity and demyelination via chemokine release and antigen presentation.
Specimen part
View SamplesDetermination of the mechanism by which fibrinogen, a central blood coagulation protein drives immunological responses targeted to the CNS. Results identify the factors involved in the regulation and provide mechanistic basis.
Blood coagulation protein fibrinogen promotes autoimmunity and demyelination via chemokine release and antigen presentation.
Specimen part
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