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GSE81246
Homo sapiens
48 Downloadable Samples
Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Primary human cytomegalovirus (HCMV) infection usually goes unnoticed, causing mild or no symptoms in immunocompetent individuals. Some rare severe clinical cases have however been reported without investigation of host immune responses or viral virulence. In this present study, we investigate, for the first time, phenotypic and functional features together with gene expression profiles in immunocompetent adults experiencing a severe primary HCMV infection. Twenty PHIP were enrolled as well as 26 HCMV-seronegative and 39 HCMV-seropositive healthy controls. PHIP had a huge lymphocytosis marked by massive expansion of NK and T cell compartments. Interestingly, PHIP mounted efficient innate and adaptive immune responses with a deep HCMV imprint, revealed mainly by the expansion of NKG2C+ NK cells, CD16+ V2- T cells and conventional HCMV-specific CD8+ T cells. The main effector lymphocytes were activated and displayed an early immune phenotype that developed toward a more mature differentiated status. We suggest that both huge lymphocytosis and excessive lymphocyte activation could contribute to a massive cytokine production known to mediate tissue damage observed in PHIP. Taken together, these findings bring new insights into the comprehensive understanding of immune mechanisms involved during primary HCMV-infection in immunocompetent individuals.
Publication Title
Severe Symptomatic Primary Human Cytomegalovirus Infection despite Effective Innate and Adaptive Immune Responses.
Sample Metadata Fields
Disease
View Samples- Mus musculus
- 64 Downloadable Samples
Illumina HiSeq 1500
Description
Differentiation of haematopoietic stem cells followsa hierarchical program of transcription-factor regulated events. Early myeloid cell differentiation is dependent on PU.1 and CEBPA (CCAAT/enhancer binding protein alpha), late myeloid differentiation is orchestrated by CEBPE (CCAAT/enhancer binding protein epsilon). The influence of SWI/SNF (SWItch/Sucrose Non-Fermentable) chromatin remodelling factors as novel master regulators of haematopoietic differentiation is only beginning to be explored. Here, we identified three homozygous loss-of-function mutations in SMARCD2 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 2), a member of the SWI/SNF complex, in three unrelated pedigrees. We find that SMARCD2-deficient hematopoiesis results in dysfunctional neutrophil granulocytes, characterized by specific granule deficiency, myelodysplasia, and an excess of blast cells. We can show that SMARCD2 controls early steps in the differentiation of myeloid-erythroid progenitor cells in mice and zebra fish. In vitro SMARCD2 interacts with the transcription factor CEBPE. Furthermore, we find that SMARCD2 controls expression of neutrophil proteins stored in specific granules and leads to transcriptional and chromatin changes in AML cells. Hence, we identify SMARCD2 as a key factor controlling myelopoiesis and as a potential tumour suppressor in leukemia. Overall design: We analyzed CD45.2+ Lin- Mac+/low Sca1+ cKit+ (LSK) cells from Smarcd2 wild-type, heterozygous and mutant foetal livers in at least 5 replicates Additionally, we analysed three different progenitor populations from Smarcd2 wild-type and homozygous knock-out foetal livers: CD45+Lin-Sca-1-CD177+CD34lowCD16/32 (FCGR)low(MEP) CD45+Lin-Sca-1-CD177+CD34+CD16/32(FCGR)int (CMP) CD45+Lin-Sca-1-CD177+CD34+CD16/32(FCGR)high (GMP)
Publication Title
Chromatin-remodeling factor SMARCD2 regulates transcriptional networks controlling differentiation of neutrophil granulocytes.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Rattus norvegicus
- 22 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
AhR activation underlies the CYP1A autoinduction by A-998679 in rats.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Male Sprague-Dawley rats [Crl:CD(SD)IGS BR], weighing ~250 g at study initiation were obtained from Charles River Laboratories, Inc. (Wilmington, MA). Rats were housed singly in ventilated, stainless steel, wire-bottom hanging cages and fed non-certified Rodent Chow (Harlan Labs, Madison, WI) and water ad libitum and acclimated for at least 5 days after arrival. Rats were randomly assigned to various treatment groups (3 rats/group) and were dosed once daily by oral gavage with vehicle (0.2% hydroxypropylmethylcellulose at a dose volume of 10 ml/kg) or with 30, 100, or 200 mg/kg of A-998679. All rats were fasted overnight after their last dose, weighed and sacrificed under isoflurane anesthesia. Liver and small intestine (jejunum) were flash frozen in liquid nitrogen and stored at 80C until processing for gene expression profiling on the Affymetrix platform.
Publication Title
AhR activation underlies the CYP1A autoinduction by A-998679 in rats.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 10 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Male Sprague-Dawley rats [Crl:CD(SD)IGS BR], weighing ~250 g at study initiation were obtained from Charles River Laboratories, Inc. (Wilmington, MA). Rats were housed singly in ventilated, stainless steel, wire-bottom hanging cages and fed non-certified Rodent Chow (Harlan Labs, Madison, WI) and water ad libitum and acclimated for at least 5 days after arrival. Rats were randomly assigned to various treatment groups (3 rats/group) and were dosed once daily by oral gavage with vehicle (0.2% hydroxypropylmethylcellulose at a dose volume of 10 ml/kg) or with 30, 100, or 200 mg/kg of A-998679. All rats were fasted overnight after their last dose, weighed and sacrificed under isoflurane anesthesia. Liver and small intestine (jejunum) were flash frozen in liquid nitrogen and stored at 80C until processing for gene expression profiling on the Affymetrix platform.
Publication Title
AhR activation underlies the CYP1A autoinduction by A-998679 in rats.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Danio rerio
- 9 Downloadable Samples
- IlluminaHiSeq2500
Description
Goal of this study is differential gene expression between wild type and MZnanog mutant during early zebrafish embryogenesis Overall design: Three timepoints - 2 hours post fertilization (hpf), 4 hpf, and 6.5 hpf; two replicates of wild type at each time point, one replicate for MZnanog at each time point
Publication Title
The primary role of zebrafish <i>nanog</i> is in extra-embryonic tissue.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 8 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
In Saccharomyces cerevisiae, the maturation of both pre-rRNA and pre-small nucleolar RNAs (pre-snoRNAs) involves common factors, thereby providing a potential mechanism for the coregulation of snoRNA and rRNA synthesis. In this study, we examined the global impact of the double-stranded-RNA-specific RNase Rnt1p, which is required for pre-rRNA processing, on the maturation of all known snoRNAs. In silico searches for Rnt1p cleavage signals, and genome-wide analysis of the Rnt1p-dependent expression profile, identified seven new Rnt1p substrates. Interestingly, two of the newly identified Rnt1p-dependent snoRNAs, snR39 and snR59, are located in the introns of the ribosomal protein genes RPL7A and RPL7B. In vitro and in vivo experiments indicated that snR39 is normally processed from the lariat of RPL7A, suggesting that the expressions of RPL7A and snR39 are linked. In contrast, snR59 is produced by a direct cleavage of the RPL7B pre-mRNA, indicating that a single pre-mRNA transcript cannot be spliced to produce a mature RPL7B mRNA and processed by Rnt1p to produce a mature snR59 simultaneously. The results presented here reveal a new role of yeast RNase III in the processing of intron-encoded snoRNAs that permits independent regulation of the host mRNA and its associated snoRNA.
Publication Title
Genome-wide prediction and analysis of yeast RNase III-dependent snoRNA processing signals.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Histone deacetylases (Hdac) remove acetyl groups from proteins, influencing global and specific gene expression. Hdacs control inflammation, as shown by Hdac inhibitor-dependent protection from DSS-induced murine colitis. While tissue-specific Hdac knockouts show redundant and specific functions, little is known of their intestinal epithelial cell (IEC) role. We have shown previously that dual Hdac1/Hdac2 IEC-specific loss disrupts cell proliferation and determination, with decreased secretory cell numbers and altered barrier function. We thus investigated how compound Hdac1/Hdac2 or Hdac2 IEC-specific deficiency alters the inflammatory response. Floxed Hdac1 and Hdac2 and villin-Cre mice were interbred. Compound Hdac1/Hdac2 IEC-deficient mice showed chronic basal inflammation, with increased basal Disease Activity Index (DAI) and deregulated Reg gene colonic expression. DSS-treated dual Hdac1/Hdac2 IEC-deficient mice displayed increased DAI, histological score, intestinal permeability and inflammatory gene expression. In contrast to double knockouts, Hdac2 IEC-specific loss did not affect IEC determination and growth, nor result in chronic inflammation. However, Hdac2 disruption protected against DSS colitis, as shown by decreased DAI, intestinal permeability and caspase-3 cleavage. Hdac2 IEC-specific deficient mice displayed increased expression of IEC gene subsets, such as colonic antimicrobial Reg3b and Reg3g mRNAs, and decreased expression of immune cell function-related genes. Our data show that Hdac1 and Hdac2 are essential IEC homeostasis regulators. IEC-specific Hdac1 and Hdac2 may act as epigenetic sensors and transmitters of environmental cues and regulate IEC-mediated mucosal homeostatic and inflammatory responses. Different levels of IEC Hdac activity may lead to positive or negative outcomes on intestinal homeostasis during inflammation
Publication Title
The acetylome regulators Hdac1 and Hdac2 differently modulate intestinal epithelial cell dependent homeostatic responses in experimental colitis.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 169 Downloadable Samples
- IonTorrentProton
Description
We explored mechanisms of carcinogenicity of acrylamide in the rat thyroid. We compared the transcriptome profiles of target(thyroid) vs non-target(liver) tissues.
Publication Title
Transcriptional profiling of male F344 rats suggests the involvement of calcium signaling in the mode of action of acrylamide-induced thyroid cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Dose and time course response of lapatinib in breast cancer cell lines.
Publication Title
Delineation of molecular mechanisms of sensitivity to lapatinib in breast cancer cell lines using global gene expression profiles.
Sample Metadata Fields
Disease, Disease stage, Cell line, Compound, Time
View Samples