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GSE26488
Mus musculus
21 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Abstract of publicaton: CD4/CD8 double-positive (DP) thymocytes express the transcriptional repressor Histone Deacetylase 7 (HDAC7), a class IIa HDAC that is exported from the cell nucleus after T cell receptor (TCR) engagement. Through signal-dependent nuclear export, class IIa HDACs such as HDAC7 mediate signal-dependent changes in gene expression that are important to developmental fate decisions in multiple tissues. We report that HDAC7 is exported from the cell nucleus during positive selection in thymocytes, and regulates genes mediating the coupling between TCR engagement and downstream events that determine cell survival. Thymocytes lacking HDAC7 are inefficiently positively selected due to a severely shortened lifespan and exhibit a truncated repertoire of TCR Jalpha segments. The expression of multiple important mediators and modulators of the response to TCR engagement is altered in HDAC7-deficient thymocytes, resulting in increased tonic MAP kinase activity that contributes to the observed loss of viability. Remarkably, the activity of Protein Kinase D, the kinase that mediates nuclear export of HDAC7 in response to TCR signaling, is also increased in HDAC7-deficient thymocytes, suggesting that HDAC7 nuclear export governs a self-sustaining auto-excitatory loop. These experiments add to the understanding of the life/death decision in thymic T cell development, define a novel function for class IIa HDACs, and point to a novel feed-forward mechanism whereby these molecules regulate their own state and mediate stable developmental transitions. Title of manuscript: Nuclear Export of Histone Deacetylase 7 During Thymic Selection Mediates Immune Self-tolerance. abstract of manuscript: Histone Deacetylase 7 (HDAC7) is a TCR signal-dependent regulator of differentiation that is highly expressed in CD4/CD8 double-positive (DP) thymocytes. Here we examine the effect of blocking TCR-dependent nuclear export of HDAC7 during thymic selection, through expression of a signal-resistant mutant of HDAC7 (HDAC7-?P) in thymocytes. We find that HDAC7-?P Transgenic thymocytes exhibit a profound block in negative thymic selection, but can still undergo positive selection, resulting in the escape of autoreactive T cells into the periphery. Gene expression profiling reveals a comprehensive suppression of the negative selection-associated gene expression program in DP thymocytes, associated with a defect in the activation of MAP kinase pathways by TCR signals. The consequence of this block in vivo is a lethal autoimmune syndrome involving the exocrine pancreas and other abdominal organs. These experiments establish a novel molecular model of autoimmunity and cast new light on the relationship between thymic selection and immune self-tolerance. Goal of Microarray experiment: We did these experiments to determine how alteration of the function of HDAC7, a site-specific and signal-dependent repressor of transcription, changes gene expression in CD4/CD8 DP thymocytes.
Publication Title
Histone deacetylase 7 regulates cell survival and TCR signaling in CD4/CD8 double-positive thymocytes.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We used microarrays to detail the global programme of gene expression underlying the loss of CD28 co-receptor on primary human CD8+ T cells.
Publication Title
Metabolic reprogramming of human CD8<sup>+</sup> memory T cells through loss of SIRT1.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 48 Downloadable Samples
- Illumina mouseRef-8 v1.1 expression beadchip
Description
A/J mice are genetically predisposed to spontaneous and/or chemically-induced lung tumors while C57BL/6J (B6) mice are resistant. This genetic disparity provides a unique scenario to identify molecular mechanisms associated with the lung response to welding fume at the transcriptome level.
Publication Title
Response of the mouse lung transcriptome to welding fume: effects of stainless and mild steel fumes on lung gene expression in A/J and C57BL/6J mice.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This experiment was conducted to test multiple hypotheses: 1) long-wave 365 nm UV light exposure at low fluences does not alter gene expression of hMSC, 2) presence of radical species during polymerization causes DNA damage in hMSC, 3) 3D encapsulation of hMSC causes changes in gene expression of hMSC compared with traditional 2D culture, 4) Differencesin 3D hydrogel networks induce gene expression changes in hMSC
Publication Title
Low-Dose, Long-Wave UV Light Does Not Affect Gene Expression of Human Mesenchymal Stem Cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The aim of the experiment was to compare to single and combined effect of Ikaros activation and IL-7 withdrawal in the Ikaros-null pre-B cell line BH1
Publication Title
Ikaros is absolutely required for pre-B cell differentiation by attenuating IL-7 signals.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 14 Downloadable Samples
Illumina HiSeq 2000
Description
Recent revelations into microRNA function suggest that microRNAs serve as a key player in a robust adaptive response against stress in animals through their fine-tuning capability in gene expression. However, it remains largely unclear how a microRNA-modulated downstream mechanism contributes to the process of homeostatic adaptation. Here we show that loss of an intestinally expressed microRNA gene mir-60 in the nematode C. elegans promotes adaptive response against oxidative stress; animals lacking mir-60 dramatically extend lifespan under a mild and long-term oxidative stress condition, while they do not increase resistance against a strong and transient oxidative stress exposure. We found that canonical stress responsive factors, such as DAF-16/FOXO, are dispensable for mir-60 loss to enhance oxidative stress resistance. Gene expression profiles revealed that genes encoding lysosomal proteases and those involved in the xenobiotic metabolism and pathogen defense response are up-regulated by the mir-60 loss. Detailed genetic studies and computational microRNA target prediction suggest that endocytosis components and a bZip transcription factor gene zip-10, which functions in innate immune response, are directly modulated by miR-60 in the intestine. Our findings suggest that the mir-60 loss facilitates adaptive response against chronic oxidative stress by ensuring the maintenance of cellular homeostasis. Overall design: To identify genes that respond to the mir-60 loss, RNA expression profiles were examined between the mir-60 loss mutant (mir-60(n4947)) and its control animals using the high-throughput sequencing technology. In this study, we used spe-9(hc88), a temperature-sensitive sterile strain, which has been shown in previous studies to have a lifespan similar to wild-type and widely used in gene expression studies to reduce the effect of RNA contamination from younger progenies. Both spe-9 single and mir-60;spe-9 double mutant animals were cultured at a restrictive temperature 23.5 °C, and treated with paraquat 5 mM during adulthood for chronic oxidative stress. Total RNAs were purified at the following time points: Day 0 young adult for both spe-9 and mir-60;spe-9 (just before paraquat exposure); Day 7 for both spe-9 and mir-60;spe-9 (50% survival time for spe-9); Day 10 for mir-60;spe-9 (50% survival time for mir-60;spe-9). For Day 0 controls, total RNAs were isolated twice independently for biological replicates. cDNA libraries were made for these 7 samples with indexed adapters using TruSeq Stranded mRNA Sample Prep Kit (Illumina), and sequenced on 2 lanes of flow cells on the HiSeq 2000/2500 platform, eventually providing 14 sequencing samples.
Publication Title
An intestinal microRNA modulates the homeostatic adaptation to chronic oxidative stress in <i>C. elegans</i>.
Sample Metadata Fields
Specimen part, Treatment, Subject, Time
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
MED23, a subunit of the Mediator coactivator complex, is important for the expression of a subset of MAPK/ERK pathway-dependent target genes; however, the genes in this subset varies between cell types. MAPK/ERK pathway-dependent processes are essential for T-cell development and function, but whether MED23 has a role in this context is unknown. We generated Med23 conditional knockout mice and induced Med23 deletion in early T cell development using the lineage specific Lck-Cre transgene. While the total cell number and distribution of cell populations in the thymuses of Med23flox/flox;Lck-Cre mice were essentially normal, MED23 null T-cells failed to efficiently populate the peripheral lymphoid organs. MED23 null thymocytes displayed decreased expression of the MAPK/ERK-responsive genes Egr1, Egr2, as well as of the membrane glycoprotein Cd52 (CAMPATH-1). MED23 null CD4 single-positive thymocytes also showed decreased expression of KLF2 (LKLF), a T cell master regulatory transcription factor. Indeed, similarities between the phenotypes of mice lacking MED23 or KLF2 in T-cells suggest that KLF2 deficiency in MED23 null T-cells is one of their key defects. Mechanistic experiments using MED23 null MEFs further suggest that MED23 is required for full activity of the MAPK-responsive transcription factor MEF2, which has previously been shown to mediate Klf2 expression. In summary, our data indicate that MED23 has critical roles in enabling T-cells to populate the peripheral lymphoid organs, possibly by potentiating MEF2-dependent expression of the T-cell transcription factor KLF2.
Publication Title
T-cells null for the MED23 subunit of mediator express decreased levels of KLF2 and inefficiently populate the peripheral lymphoid organs.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
XBP1 is a transcription factor that is induced by unconventional splicing associated with endoplasmic reticulum stress and plays a role in development of liver and plasma cells. We previously reported that brain derived neurotrophic factor (BDNF) leads to splicing of XBP1 mRNA in neurites, and that XBP1 is required for BDNF-induced neurite extension and branching. To search for the molecular mechanisms of how XBP1 plays a role in neural development, comprehensive gene expression analysis was performed in primary telencephalic neurons obtained from Xbp1 knockout mice at embryonic day 12.5. By searching for the genes induced by BDNF in wild type neurons but this induction was reduced in Xbp1 knockout mice, we found that upregulation of three GABAergic markers, somatostatin (Sst), neuropeptide Y (Npy), and calbindin (Calb1), were compromised in Xbp1 knockout neurons. Attenuated induction of Npy and Calb1 was confirmed by quantitative RT-PCR. In neurons lacking in Xbp1, upregulation of GABAergic markers was attenuated. Impaired BDNF-induced neurite extension in Xbp1 knockout neurons might be mediated by disturbed BDNF-induced differentiation of GABAergic interneurons.
Publication Title
Attenuated BDNF-induced upregulation of GABAergic markers in neurons lacking Xbp1.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Differentiation of human skeletal stem cells (hMSC) into osteoblasts is regulated by a few well described transcription factors. Our study used clustering and gene expression data to identify a novel transcription factor. ZNF25, which we showed is involved in osteoblast differentiation.
Publication Title
Transcription factor ZNF25 is associated with osteoblast differentiation of human skeletal stem cells.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Effect of absence of interaction with MHC class II on memory CD4 T cells
Publication Title
Noncognate interaction with MHC class II molecules is essential for maintenance of T cell metabolism to establish optimal memory CD4 T cell function.
Sample Metadata Fields
Sex, Specimen part
View Samples