Celiac disease is an intestinal inflammatory disorder induced by dietary gluten in genetically susceptible individuals. The mechanisms underlying the massive expansion of interferon gproducing intraepithelial cytotoxic T lymphocytes (CTLs) and the destruction of the epithelial cells lining the small intestine of celiac patients have remained elusive. We report massive oligoclonal expansions of intraepithelial CTLs that exhibit a profound genetic reprogramming of natural killer (NK) functions. These CTLs aberrantly expressed cytolytic NK lineage receptors, such as NKG2C, NKp44, and NKp46, which associate with adaptor molecules bearing immunoreceptor tyrosine-based activation motifs and induce ZAP-70 phosphorylation, cytokine secretion, and proliferation independently of T cell receptor signaling. This NK transformation of CTLs may underlie both the self-perpetuating, gluten-independent tissue damage and the uncontrolled CTL expansion leading to malignant lymphomas in severe forms of celiac disease. Because similar changes were detected in a subset of CTLs from cytomegalovirus-seropositive patients, we suggest that a stepwise transformation of CTLs into NK-like cells may underlie immunopathology in various chronic infectious and inflammatory diseases.
Reprogramming of CTLs into natural killer-like cells in celiac disease.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Continuous expression of the transcription factor e2-2 maintains the cell fate of mature plasmacytoid dendritic cells.
Specimen part, Cell line, Time
View SamplesAstrocytes, the most prominent glial cell type in the brain, send specialized processes called endfeet around blood vessels and express a large molecular repertoire regulating the cerebrovascular system physiology. One of the most striking properties of astrocyte endfeet is their enrichment in gap junction protein Connexin 43 and 30 (Cx43 and Cx30) allowing in particular for direct intercellular trafficking of ions and small signaling molecules through perivascular astroglial networks. In this study, we addressed the specific role of Cx30 at the gliovascular interface. Using an inactivation mouse model for Cx30 (Cx30?/?), we showed that absence of Cx30 does not affect blood-brain barrier (BBB) organization and permeability. However, it results in the cerebrovascular fraction, in a strong upregulation of Sgcg encoding g-Sarcoglycan (SG), a member of the Dystrophin-associated protein complex (DAPC) connecting cytoskeleton and the extracellular matrix. The same molecular event occurs in Cx30T5M/T5M mutated mice, where Cx30 channels are closed, demonstrating that Sgcg regulation relied on Cx30 channel functions. We further characterized the cerebrovascular Sarcoglycan complex (SGC) and showed the presence of a-, ß-, d-, ?-, e- and ?- SG, as well as Sarcospan. Altogether, our results suggest that the Sarcoglycan complex is present in the cerebrovascular system, and that expression of one of its members, g-Sarcoglycan, depends on Cx30 channels. As described in skeletal muscles, the SGC may contribute to membrane stabilization and signal transduction in the cerebrovascular system, which may therefore be regulated by Cx30 channel-mediated functions. Overall design: Comparison of 3-month-old Cx30 deleted mice against WT genetic background.
The Sarcoglycan complex is expressed in the cerebrovascular system and is specifically regulated by astroglial Cx30 channels.
No sample metadata fields
View SamplesTranscriptome comparison of the winter malting barley '88Ab536' with the spring malting variety 'Morex' at two time points of the malting process: 'out of steeping' and '3 days of germination'. Three replicates of each genotype and time point were accomplished. ****[PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor, Maria Munoz-Amatriain. The equivalent experiment is BB76 at PLEXdb.]
Structural and functional characterization of a winter malting barley.
Age, Specimen part
View SamplesBreast cancer (BC) is the most commonly diagnosed neoplasm in women worldwide and a well-recognized heterogeneous pathology classified into four molecular subtypes: Luminal A, Luminal B, HER2-enriched and Basal-like, each one with different biological and clinical characteristics. It is well recognize that clinical and molecular heterogeneity of BC is driven in part by mRNA and lncRNAs. We profiled mRNAs and lncRNA in 75 adjuvant tumors using an Affymetrix microarray platform.
A lncRNA landscape in breast cancer reveals a potential role for AC009283.1 in proliferation and apoptosis in HER2-enriched subtype.
Specimen part
View SamplesWe silenced lncRNA AC009283.1 using shRNAs in cell line SKBR3, carried a ~75% silencing compared to thenegative control (NC).
A lncRNA landscape in breast cancer reveals a potential role for AC009283.1 in proliferation and apoptosis in HER2-enriched subtype.
Cell line
View SamplesHuman alveolar epithelial cells were exposed to cigarette smoke extract (CSE) for 1, 3 and 5 weeks at 1%, 5% and 10%, and gene expression was evaluated by complete transcriptome microarrays.
Cigarette Smoke Enhances the Expression of Profibrotic Molecules in Alveolar Epithelial Cells.
Cell line, Time
View SamplesAnalysis of expression profiles of human pDC cell line (CAL1) compared to an immature T cell line (MOLT4)
Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development.
No sample metadata fields
View SamplesAnalysis of expression profiles of pDCs from wild type and heterozygous E2-2 mice. Results show the control by E2-2 of the expression of pDC-enriched genes.
Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development.
No sample metadata fields
View SamplesSuper-enhancers (SEs) are clusters of enhancers that cooperatively assemble a high density of transcriptional apparatus to drive robust expression of genes with prominent roles in cell identity. We recently proposed that a phase-separated multi-molecular assembly underlies the formation and function of SEs. Here, we demonstrate that the SE-enriched factors BRD4 and MED1 form nuclear puncta that occur at SEs and exhibit properties of liquid-like condensates. Disruption of BRD4 and MED1 puncta by 1,6-hexanediol is accompanied by a loss of BRD4 and MED1 at SEs and a loss of RNAPII from SE-driven genes. We find that the intrinsically disordered regions (IDRs) of BRD4 and MED1 are sufficient to form phase-separated droplets in vitro and the MED1 IDR promotes phase separation in living cells. The MED1 IDR droplets are capable of compartmentalizing BRD4 and other transcriptional machinery in nuclear extracts. These results support the idea that SEs form phase-separated condensates that compartmentalize the transcription apparatus at key genes, provide insights into the role of cofactor IDRs in this process, and offer new insights into mechanisms involved in control of key cell identity genes. Overall design: polyA RNA-Seq in mouse embryonic stem cells
Coactivator condensation at super-enhancers links phase separation and gene control.
Specimen part, Subject
View Samples