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Mus musculus
16 Downloadable Samples
Illumina HiSeq 2500
Description
T follicular helper (TFH) cells promote affinity maturation of B cells in germinal centers (GCs), whereas T follicular regulatory (TFR) cells limit GC reaction. Store-operated Ca2+ entry (SOCE) through Ca2+ release-activated Ca2+ (CRAC) channels mediated by STIM and ORAI proteins is a fundamental signaling pathway in T lymphocytes. Here we show that SOCE is required for the differentiation and function of both TFH and TFR cells. Conditional deletion of Stim1 and Stim2 genes in T cells or Treg cells results in spontaneous autoantibody production and humoral autoimmunity. Conversely, antibody-mediated immune responses following viral infection critically depend on SOCE in TFH cells. Mechanistically, STIM1 and STIM2 control early TFR and TFH cell differentiation through NFAT-mediated IRF4, BATF and Bcl-6 expression. SOCE plays a dual role in GC response by controlling TFH and TFR cell function, thus enabling protective B cell responses and preventing humoral autoimmunity. Overall design: RNAseq analyses of WT and Stim1Stim2 DKO follicular T cells and non-follicular T cells; 4-6 mice per cohort in duplicates. Mice were infected for 10 days with LCMV.
Publication Title
Store-Operated Ca(2+) Entry in Follicular T Cells Controls Humoral Immune Responses and Autoimmunity.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
T-cell acute lymphoblastic leukemia (T-ALL) is a malignancy of T cell progenitors that in most patients is associated with activating mutations in the NOTCH1 pathway. Recent reports have indicated a link between Ca2+ homeostasis in the endoplasmic reticulum (ER), the regulation of NOTCH1 signaling and T-ALL. Here we investigated the role of store-operated Ca2+ entry (SOCE) in T-ALL. SOCE is a Ca2+ influx pathway that is mediated by the plasma membrane Ca2+ channel ORAI1 and its activators STIM1 and STIM2. Deletion of STIM1 and STIM2 in leukemic cells abolished SOCE and significantly prolonged the survival of mice in a NOTCH1-driven model of T-ALL. The survival advantage was unrelated to leukemia development and leukemic cell burden, but was associated with the SOCE-dependent ability of malignant T lymphoblasts to cause inflammation in leukemia-infiltrated organs. Mice with wildtype T-ALL showed a severe necroinflammatory response in their bone marrow, which was absent in mice with Stim1/2-/- leukemia. Several signaling pathways previously linked to cancer-induced inflammation were downregulated in Stim1/2-/- leukemic cells, likely accounting for less aggressive leukemia progression and prolonged survival of mice. Our study shows that T-ALL is associated with inflammation of leukemia-infiltrated organs and that SOCE controls the proinflammatory effects of leukemic T lymphoblasts. Overall design: Bone marrow leukemic cell were isolated from WT and Stim1/2-/- leukemic mice, 21 days after leukemia induction and their mRNA profiles were generated by deep sequencing, in triplicate.
Publication Title
STIM1 and STIM2 Mediate Cancer-Induced Inflammation in T Cell Acute Lymphoblastic Leukemia.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Influence of STIM1 on the transcriptome of CD4+ T cell subsets
Publication Title
STIM1 controls T cell-mediated immune regulation and inflammation in chronic infection.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Triggering of B cell receptors (BCR) induces a massive synthesis of NFATc1 in splenic B cells. By inactivating the Nfatc1 gene and re-expressing NFATc1 we show that NFATc1 levels are critical for the survival of splenic B cells upon BCR stimulation. NFATc1 ablation led to decreased BCR-induced Ca++ flux and proliferation of splenic B cells, increased apoptosis and suppressed germinal centre formation and immunoglobulin class switch by T cell-independent antigens. By controlling IL-10 synthesis in B cells, NFATc1 supported the proliferation and IL-2 synthesis of T cells in vitro and appeared to contribute to the mild clinical course of Experimental Autoimmune Encephalomyelitis in mice bearing NFATc1-/- B cells. These data indicate NFATc1 as a key factor controlling B cell function.
Publication Title
NFATc1 affects mouse splenic B cell function by controlling the calcineurin--NFAT signaling network.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Influence of ovarian stimulation with 200 IU of hCG, (administered in the late follicular phase among ICSI patients undergoing a GnRH-antagonist protocol), on the endometrium on the day of oocyte pick-up.
Publication Title
Gene expression profile in the endometrium on the day of oocyte retrieval after ovarian stimulation with low-dose hCG in the follicular phase.
Sample Metadata Fields
Specimen part, Treatment
View Samples
GSE13027- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In GnRH-antagonist/rec-FSH stimulated cycles, advanced endometrial maturation on the day of oocyte retrieval correlates with altered gene expression
Publication Title
In GnRH antagonist/rec-FSH stimulated cycles, advanced endometrial maturation on the day of oocyte retrieval correlates with altered gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples GSE19959- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Premature progesterone (P) rise during GnRH antagonist cycles for IVF is a frequent phenomenon and has been associated with lower pregnancy and implantation rates. Different thresholds of progesterone have been used so far to define its premature rise during the follicular phase of an IVF stimulated cycle. In this study, we evaluated endometrial gene expression on the day of oocyte retrieval according to the level of serum progesterone on the day of hCG administration in GnRH antagonist cycles.Endometrial biopsies from eleven patients were taken with a Pipelle de Cornier (Prodimed, Neuilly-en-Thelle, France) on the day of oocyte retrieval in a GnRH antagonist/rec-FSH stimulated IVF cycle with fresh embryo transfer. Biopsies were analysed for gene expression with Affymetrix Human Genome (HG) U133 Plus 2.0 Arrays and GCOS software (Affymetrix, Santa Clara, CA, USA). Patients were divided into three different groups according to their progesterone serum concentration on the day of hCG administration (A) P <= 0.9 ng/mL, (B) 1 < P < 1.5 ng/mL, and (C) P > 1.5 ng/mL. Serum P was measured with the automated Elecsys immunoanalyser (Roche Diagnostics, Mannheim, Germany). Selected differentially expressed genes were validated with quantitative real-time PCR (QPCR) with TaqMan Gene Expression Assays (Applied Biosystems, Foster City, CA, USA).
Publication Title
Progesterone rise on HCG day in GnRH antagonist/rFSH stimulated cycles affects endometrial gene expression.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
CONTEXT Nowadays, the molecular mechanisms involved in endometrial receptivity and implantation are still not clear.
Publication Title
Cyclooxygenase-2 network as predictive molecular marker for clinical pregnancy in in vitro fertilization.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Influence of ovarian stimulation with 200 IU of hCG, (administered in the late follicular phase among ICSI patients undergoing a GnRH-antagonist protocol), on the endometrium on the day of oocyte pick-up.
Publication Title
Cyclooxygenase-2 network as predictive molecular marker for clinical pregnancy in in vitro fertilization.
Sample Metadata Fields
Specimen part
View Samples