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SRP069082
Mus musculus
6 Downloadable Samples
Illumina Genome Analyzer IIx
Description
Multipotent pancreatic progenitors (MPC) are defined as Ptf1a+, Mychigh, Cpa+ cells. During the transition from MPC to unipotent acinar progenitors, c-Myc is down-regulated whereas Ptf1a is up-regulated, leading to the deployment of the acinar program. Here, we show that c-Myc and Ptf1a interact directly and c-Myc binds to, and represses, the transcriptional activity of the PTF1 complex in vitro and in vivo. Using Ela1-Myc mice, in which c-Myc is overexpressed in acinar cells starting at E14.5, we find that acinar cells fail to undergo normal maturation at P1 and this is followed by a massive subsequent repression of the acinar programme. Lineage tracing with Ptf1aCreERT2;Rosa26YFP and Ela1-Myc;Ptf1aCreERT2;Rosa26YFP mice receiving TMX at E15.5 and analyzed at E18.5 revealed that c-Myc overexpression is associated with activation of a hepatic programme but not with pancreatic lineage misspecification At 8 weeks, the silencing of the acinar program is associated with increased expression of the PRC2 complex in a c-Myc dependent manner. Genome wide studies show that Ptf1a and c-Myc display partially overlapping chromatin occupancy patterns and DNA binding competition. We conclude that c-Myc down-regulation during development is crucial for the maturation of pre-acinar to acinar cells. c-Myc overexpression may contribute to pancreatic carcinogenesis by restraining cell differentiation and rendering cells susceptible to transformation. Overall design: Pancreas mRNA profiles of 8-week old wild type (WT) and ELA1-MYC mice were generated by deep sequencing, in triplicate, using Illumina GAIIx.
Publication Title
c-Myc downregulation is required for preacinar to acinar maturation and pancreatic homeostasis.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used microarrays to detail the global programme of gene expression by circulating TCRVgamma9+ gamma delta T cells isolated from healthy individuals,tested either as resting cells or cells activated by phosphoantigen BrHPP and IL-2at an early(+6hrs) and a late (+7days) timepoint.
Publication Title
The gene expression profile of phosphoantigen-specific human γδ T lymphocytes is a blend of αβ T-cell and NK-cell signatures.
Sample Metadata Fields
Specimen part, Disease, Treatment, Subject, Time
View Samples- Mus musculus
- 48 Downloadable Samples
- NextSeq 500
Description
To udnderstand the tissue-resident features of antigen-specific memory T cells of the bone marrow and spleen, we performed RNA-Seq and compared expression levels of genes of resting LCMV.GP66-77 specific CD4 T cells isolated from bone marrow (BM) and spleen of LCMV.GP61-80 primed C57BL/6 mice. Overall design: C57BL/6 mice were primed at day 0 with LCMV.GP61-80-NP-MSA + poly(I:C) and immunized again at day 14 with LCMV.GP61-80 + poly(I:C). Sixty days after the last immunization mice were sacrificed and LCMV.GP66–77-specific CD69+ and CD69- memory CD4 T cells were isolated from BM and spleen.
Publication Title
CD69<sup>+</sup> memory T lymphocytes of the bone marrow and spleen express the signature transcripts of tissue-resident memory T lymphocytes.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Identification of key regions and genes important in the pathogenesis of sezary syndrome by combining genomic and expression microarrays.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
This study used tumour and paired normal samples from 28 Szary Syndrome (SS) patients to define recurrent regions of chromosomal aberrations. Our data identified recurrent losses of 17p13.2-p11.2 and 10p12.1-q26.3 occurring in 71 and 68% of cases respectively; common gains were detected for 17p11.2-q25.3 (64%) and chromosome 8/8q (50%). Moreover, we identified novel genomic lesions recurring in more than 30% of tumours: loss of 9q13-q21.33 and gain of 10p15.3-10p12.2. In the Szary Syndrome cases analysed, we could find several small and few large Uniparental Disomies involving interstitial or telomeric regions of LOH occurring mainly for chromosome 10 and to a lesser extent for chromosome 9 and 17. In the attempt to correlate Copy Number data and clinical parameters we find a relationship between complex pattern of chromosomal aberrations, involving at least three recurrent Copy Number alterations, and shorter survival. Integrating mapping and transcriptional data we were able to identify a total of 113 deregulated transcripts in aberrant chromosomal regions that included cancer related genes such as members of the NF-kB pathway (BAG4, BTRC, NKIRAS2, PSMD3, TRAF2) that might explain its constitutive activation in CTCL. Matching this list of genes with those discriminating patients with different survival times we identify several common candidates that might exert critical roles in Szary Syndrome, like BUB3 and PIP5K1B.
Publication Title
Identification of key regions and genes important in the pathogenesis of sezary syndrome by combining genomic and expression microarrays.
Sample Metadata Fields
Specimen part, Disease
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
Myocardin-related transcription factors (MRTFs) play a central role in the regulation of actin expression and cytoskeletal dynamics. Stimuli that promote actin polymerization allow for shuttling of MRTFs to the nucleus where they activate serum response factor (SRF), a regulator of actin and other cytoskeletal protein genes. SRF is an essential regulator of skeletal muscle differentiation and numerous components of the muscle sarcomere, but the potential involvement of MRTFs in skeletal muscle development has not been examined. We explored the role of MRTFs in muscle development in vivo by generating mutant mice harboring a skeletal muscle-specific deletion of MRTF-B and a global deletion of MRTF-A. These double knockout (dKO) mice were able to form sarcomeres during embryogenesis. However, the sarcomeres were abnormally small and disorganized, causing skeletal muscle hypoplasia and perinatal lethality. Transcriptome analysis demonstrated dramatic dysregulation of actin genes in MRTF dKO mice, highlighting the importance of MRTFs in actin cycling and myofibrillogenesis. MRTFs were also necessary for the survival of skeletal myoblasts and for the efficient formation of intact myotubes. Our findings reveal a central role for MRTFs in sarcomere formation during skeletal muscle development and point to the potential involvement of these transcriptional coactivators in skeletal myopathies. Overall design: Gene expression profile was generated comparing wild type (WT) and HSA-Cre, MRTF-A/B double knockout mice, by deep seqencing, with three biological replicates, using Illumina HiSeq 2500.
Publication Title
Myocardin-related transcription factors are required for skeletal muscle development.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
The integration of positive and negative intra- and extra-cellular signals dictates whether a cell will proliferate or differentiate. While it is intuitive to speculate that nutrients availability may influence this alternative, a comprehensive complement of the molecular determinants involved in this process has not been elucidated yet. In this study, we will investigate how nutrients (glucose) affect skeletal myogenesis. C2C12 cells will be cultured in high glucose and low glucose conditions, and their differenciation will be studied.
Publication Title
Glucose restriction inhibits skeletal myoblast differentiation by activating SIRT1 through AMPK-mediated regulation of Nampt.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
Myocardin-Related Transcription Factors A and B (MRTF-A and MRTF-B) are highly homologous proteins that function as powerful coactivators of serum response factor (SRF), a ubiquitously expressed transcription factor essential for cardiac development. The SRF/MRTF complex binds to CArG boxes found in the control regions of genes that regulate cytoskeletal dynamics and muscle contraction, among other processes. While SRF is required for heart development and function, the role of MRTFs in the developing or adult heart has not been explored. Through cardiac-specific deletion of MRTF alleles in mice, we show that either MRTF-A or MRTF-B is dispensable for cardiac development and function, whereas deletion of both MRTF-A and MRTF-B causes a spectrum of structural and functional cardiac abnormalities. Defects observed in MRTF-A/B null mice ranged from reduced cardiac contractility and adult onset heart failure to neonatal lethality accompanied by sarcomere disarray. RNA-seq analysis on neonatal hearts identified the most altered pathways in MRTF double knockout hearts as being involved in cytoskeletal organization. Together, these findings demonstrate redundant but essential roles of the MRTFs in maintenance of cardiac structure and function and as indispensible links in cardiac cytoskeletal gene regulatory networks. Overall design: P0 Heart mRNA profiles of wild-type (WT) and MRTFA/B double knockout animals were generated in duplicate using DeepSeq using Illumina HiSeq 2500
Publication Title
Myocardin-related transcription factors are required for cardiac development and function.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Renal excretion of water and major electrolytes exhibits a significant circadian rhythm. This functional periodicity is believed to result, at least in part, from circadian changes in secretion/reabsorption capacities of the distal nephron and collecting ducts. Here, we studied the molecular mechanisms underlying circadian rhythms in the distal nephron segments, i.e. distal convoluted tubule (DCT) and connecting tubule (CNT) and, the cortical collecting duct (CCD). Temporal expression analysis performed on microdissected mouse DCT/CNT or CCD revealed a marked circadian rhythmicity in the expression of a large number of genes crucially involved in various homeostatic functions of the kidney. This analysis also revealed that both DCT/CNT and CCD possess an intrinsic circadian timing system characterized by robust oscillations in the expression of circadian core clock genes (clock, bma11, npas2, per, cry, nr1d1) and clock-controlled Par bZip transcriptional factors dbp, hlf and tef. The clock knockout mice or mice devoid of dbp/hlf/tef (triple knockout) exhibit significant changes in renal expression of several key regulators of water or sodium balance (vasopressin V2 receptor, aquaporin-2, aquaporin-4, alphaENaC). Functionally, the loss of clock leads to a complex phenotype characterized by partial diabetes insipidus, dysregulation of sodium excretion rhythms and a significant decrease in blood pressure. Collectively, this study uncovers a major role of molecular clock in renal function.
Publication Title
Molecular clock is involved in predictive circadian adjustment of renal function.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Affymetrix expression arrays were used to compare expression patterns upon knockdown of PARP-1, PARG, SIRT1, or macroH2A in comparison to Luciferase control.
Publication Title
Global analysis of transcriptional regulation by poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase in MCF-7 human breast cancer cells.
Sample Metadata Fields
No sample metadata fields
View Samples