We have develop a proteogenomics-based approach for identification of human MHC class I-associated peptides, including those deriving from polymorphisms, mutations and non-canonical reading frames Overall design: RNA-seq of human EBV-infected B lymphoblasts derived from peripheral blood mononuclear cells from volunteers Please note that GSM1641204 and GSM1641205 are reanalyzed and duplicated sample records of GSM1186811 and GSM1186812, respectively, for the convenient retrieval of the complete raw data from SRA
Global proteogenomic analysis of human MHC class I-associated peptides derived from non-canonical reading frames.
No sample metadata fields
View SamplesWe developed a novel approach combining next generation sequencing, bioinformatics and mass spectrometry to assess the impact of non-MHC polymorphisms on the repertoire of MHC I-associated peptides (MIPs). We compared the genomic landscape of MIPs eluted from B lymphoblasts of two MHC-identical siblings and determined that MIPs mirror the genomic frequency of non-synonymous polymorphisms but they behave as recessive traits at the surface level. Moreover, we showed that 11.7% of the MIP coding exome is polymorphic at the population level. Our method provides fundamental insights into the relation between the genomic self and the immune self and accelerates the discovery of polymorphic MIPs (also known as minor histocompatibility antigens), which play a major role in allo-immune responses. Overall design: RNA-seq of human B lymphoblasts derived from peripheral blood mononuclear cells from 2 HLA-identical female siblings.
Impact of genomic polymorphisms on the repertoire of human MHC class I-associated peptides.
Specimen part, Subject
View SamplesApproximately 75% of the human genome is transcribed, the majority of which does not encode protein. However, most noncoding RNA (ncRNA) is rapidly degraded after transcription, and relatively few have established functions, questioning the significance of this observation. Here we show that esBAF, a SWI/SNF family nucleosome remodeling factor, suppresses transcription of ncRNAs from approximately 57,000 nucleosome-depleted regions (NDRs) throughout the genome of mouse embryonic stem cells (ESCs). We show that esBAF functions both to keep NDRs nucleosome-free and to promote elevated nucleosome occupancy adjacent to NDRs. Reduction of adjacent nucleosome occupancy upon esBAF depletion is strongly correlated with ncRNA expression, suggesting that flanking nucleosomes form a barrier to pervasive transcription. Upon forcing nucleosome occupancy near an NDR using a nucleosome-positioning sequence, we find that esBAF is no longer required to silence transcription. These data reveal a novel role for esBAF in suppressing pervasive transcription from open chromatin regions in ESCs. Overall design: Examine nucleosome occupancy (MNase-Seq) and transcript production (CapSeq and RNA-Seq) in EGFP KD and Smarca4 KD ESCs
Suppression of pervasive noncoding transcription in embryonic stem cells by esBAF.
No sample metadata fields
View SamplesGeminin is a small nucleoprotein that neuralizes ectoderm in the Xenopus embryo. Geminin promotes neural fate acquisition of mouse embryonic stem cells: Geminin knockdown during neural fate acquisition decreased expression of neural precursor cell markers (Pax6, Sox1), while increasing expression of Pitx2, Lefty1 and Cited2, genes involved in formation of the mouse node. Here we differentiated mouse embryonic stem cells into embryoid bodies to study Geminin's ability to repress primitive streak mesendoderm fate acquisition. We used microarrays to define the sets of genes that are regulated by Geminin during cell fate acquisition in embryoid bodies, using Dox-inducible Geminin knockdown or overexpression mouse embryonic stem cell lines.
Geminin restrains mesendodermal fate acquisition of embryonic stem cells and is associated with antagonism of Wnt signaling and enhanced polycomb-mediated repression.
Specimen part
View SamplesFunctional discrimination between normal centroblast and centrocyte obtained from human inflamed tonsils after cell sorting.
CXCR4 expression functionally discriminates centroblasts versus centrocytes within human germinal center B cells.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals.
Sex, Age
View SamplesEpigenetic information can be inherited through the mammalian germline, and represents a plausible transgenerational carrier of environmental information. To test whether transgenerational inheritance of environmental information occurs in mammals, we carried out an expression profiling screen for genes in mice that responded to paternal diet.
Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals.
No sample metadata fields
View SamplesUntreated HIV-1 infection progresses through acute and asymptomatic stages to AIDS. While each of the three stages has well-known clinical, virologic and immunological characteristics, much less is known of the molecular mechanisms underlying each stage. Here we report lymphatic tissue microarray analyses revealing for the first time stage-specific patterns of gene expression during HIV-1 infection. We show that while there is a common set of key genes with altered expression throughout all stages, each stage has a unique gene-expression signature. The acute stage is most notably characterized by increased expression of hundreds of genes involved in immune activation, innate immune defenses (e.g.MDA-5, TLR-7 and -8, PKR, APOBEC3B, 3F, 3G), adaptive immunity, and in the pro-apoptotic Fas-Fas-L pathway. Yet, quite strikingly, the expression of nearly all acute-stage genes return to baseline levels in the asymptomatic stage, accompanying partial control of infection. In the AIDS stage, decreased expression of numerous genes involved in T cell signaling identifies genes contributing to T cell dysfunction. These common and stage-specific, gene-expression signatures provide new insights into the molecular mechanisms underlying the host response and the slow, natural course of HIV-1 infection.
Microarray analysis of lymphatic tissue reveals stage-specific, gene expression signatures in HIV-1 infection.
Sex, Age, Specimen part, Disease, Disease stage, Race, Subject
View SamplesTo explore events that govern the differentiation of human nave B cells (NBCs) into memory B cells and plasma cells (PCs), we designed an in vitro 2-step culture model leading non-switched NBC precursors to differentiate into two cell compartments: CD20loCD38hi and CD20+CD38+.
IL-2 requirement for human plasma cell generation: coupling differentiation and proliferation by enhancing MAPK-ERK signaling.
Specimen part, Subject, Time
View SamplesOur laboratory wanted to define the transcription profile of aged skeletal muscle. For this reason, we performed a triplicate microarray study on young (3 weeks) and aged (24 months) gatrocnemius muscle from wild-type C57B16 Mice
Transcriptional profiling of skeletal muscle reveals factors that are necessary to maintain satellite cell integrity during ageing.
Sex
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