Filters
Technology
Platform
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
- 61 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 34 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Retinoblastoma-1 (RB1), and the RB1-related proteins p107 and p130, reside at a central node in the cell cycle regulatory network. RB1 is required for normal erythroid development in vitro, but is largely dispensable for erythropoiesis in vivo. The modest phenotype caused by RB1 deficiency in mice raises questions about redundancy within the RB1 family, and the role of RB1 in erythroid differentiation. Here we show that RB1 is the major pocket protein that regulates terminal erythroid differentiation. Erythroid cells lacking all pocket proteins exhibit the same cell cycle defects as those deficient for RB1 alone. Further, we show that RB1 broadly represses gene expression in erythroid cells, coincident with the transition from precursor to terminally differentiated cell. RB1-repressed genes are well expressed but downregulated at the final stage of erythroid development. By merging differential and time-dependent changes in expression, we define a group of approximately 800 RB1-repressed genes. As anticipated, these genes are enriched for terms such as cell cycle and DNA metabolic process, but also for terms such as mRNA processing, chromosome organization, and ubiquitin-mediated protein catabolic pro-cess. Our results suggest that RB1-mediated repression of genes involved in noncanonical processes has a central role in terminal erythroid differentiation.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 27 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Retinoblastoma-1 (RB1), and the RB1-related proteins p107 and p130, reside at a central node in the cell cycle regulatory network. RB1 is required for normal erythroid development in vitro, but is largely dispensable for erythropoiesis in vivo. The modest phenotype caused by RB1 deficiency in mice raises questions about redundancy within the RB1 family, and the role of RB1 in erythroid differentiation. Here we show that RB1 is the major pocket protein that regulates terminal erythroid differentiation. Erythroid cells lacking all pocket proteins exhibit the same cell cycle defects as those deficient for RB1 alone. Further, we show that RB1 broadly represses gene expression in erythroid cells, coincident with the transition from precursor to terminally differentiated cell. RB1-repressed genes are well expressed but downregulated at the final stage of erythroid development. By merging differential and time-dependent changes in expression, we define a group of approximately 800 RB1-repressed genes. As anticipated, these genes are enriched for terms such as cell cycle and DNA metabolic process, but also for terms such as mRNA processing, chromosome organization, and ubiquitin-mediated protein catabolic pro-cess. Our results suggest that RB1-mediated repression of genes involved in noncanonical processes has a central role in terminal erythroid differentiation.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Gene expression profile of primary human CD34+/CD38lo cells differentiating along the megakaryocyte lineage.
Publication Title
Gene expression profile of primary human CD34+CD38lo cells differentiating along the megakaryocyte lineage.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 13 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Conversion of Human Gastric Epithelial Cells to Multipotent Endodermal Progenitors using Defined Small Molecules.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 13 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Endodermal stem/progenitor cells have diverse potential applications in research and regenerative medicine, so a readily available source could have widespread uses. Here we describe derivation of human induced endodermal progenitor cells (hiEndoPCs) from gastrointestinal epithelial cells using a cocktail of defined small molecules along with support from tissue-specific mesenchymal feeders. The hiEndoPCs show clonal expansion in culture and give rise to hepatocytes, pancreatic endocrine cells, and intestinal epithelial cells when treated with defined soluble molecules directing differentiation. The hiEndoPC-derived hepatocytes are able to rescue liver failure in Fah-/-Rag2-/- mice after transplantation, and, unlike hESCs, transplanted hiEndoPCs do not give rise to teratomas. Since human gastric epithelial cells are readily available from donors of many ages, this conversion strategy can generate clonally expandable cell populations with a variety of potential applications, including personalized drug screening and therapeutic strategies for liver failure and diabetes.
Publication Title
Conversion of Human Gastric Epithelial Cells to Multipotent Endodermal Progenitors using Defined Small Molecules.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Expression of the RNA-binding protein is increased upon megakaryocyte commitment, and may coordinate with mRNA stability and translation during megakaryopoiesis. Reduced expression of ATXN2 in human megakaryocytic cells decreased protein synthesis and total protein content despite equal mRNA expression. Genome-wide comparision of subpolysomal versus polysomal mRNA showed that both protein synthesis and protein degradation are derailed in absence of ATXN2. Furthermore, ATXN2 was associated with PABP and DDX6, proteins that control mRNA stability through the polyA-tail. These findings indicate that ATXN2 is involved in protein metabolism in megakaryocytes and platelet function.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 183 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
Maternal smoking has a severe negative effect on all stages of pregnancy that in consequence impairs fetal growth and development. Tobacco smoke-related defects are well established at the clinical level; however, little is known about molecular mechanisms underlying these pathological conditions. We thus employed a genomic approach to determine transcriptome alterations induced by maternal smoking in pregnancy. We assayed gene expression profiles in peripheral blood (M) leukocytes and placentas (PL) of pregnant smokers and those without significant exposure, and in cord blood (D) leukocytes of their babies. Comparative analyses defined significant deregulation of 193 genes in M cells, 329 genes in placentas, and 49 genes in D cells of smokers. These genes were mainly involved in xenobiotic metabolism, oxidative stress, inflammation, immunity, hematopoiesis, trophoblast differentiation, and vascularization. Functional annotation of the deregulated genes outlined processes and pathways affected by tobacco smoke. In smoker newborns, we identified several deregulated pathways associated with autoimmune diseases. The study demonstrates a limited ability of placenta to modulate toxic effects of maternal tobacco use at the gene expression level.
Publication Title
Transcriptome alterations in maternal and fetal cells induced by tobacco smoke.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Homo sapiens
- 104 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
Passive smoke intake by pregnant women may have detrimental effects such as spontaneous abortion, lower birth weight, stillbirth, and reduced infant lung function. To extend our knowledge on molecular effects of tobacco smoke exposure in pregnancy, we analyzed transcriptome alterations in passive smokers (PS) and compared them to those in active smokers (AS). Using Illumina Expression Beadchip with 24,526 transcript probes, gene expression patterns were assayed in placentas from PS (N=25) exposed to environmental tobacco smoke (ETS) throughout pregnancy and non-exposed (NS) counterparts (N=35), and in cord blood cells from their newborns. The ETS exposure was evaluated by questionnaire disclosure and cotinine measurement in maternal and cord bloods. A total of 196 genes were significantly deregulated in placentas of PS compared to NS. These genes were primary associated with extracellular matrix, apoptosis, blood clotting, response to stress, embryonic morphogenesis, and lipid metabolism. Cord blood of newborns of PS displayed differential expression of 116 genes encoding mainly neuronal factors, regulators of immunologic response, and protooncogenes. Gene ontology analyses highlighted some important biological processes that might be associated with placental insufficiency and fetal growth restriction in PS, such as fatty acid catabolism, coagulation, regulation of growth, and response to steroid hormone stimulus. The study demonstrates that even low dose exposure to ETS during pregnancy leads to the significant deregulation of transcriptional regulation in placental and fetal cells. The data suggest the effect of ETS on the fetus is primary indirect, mediated via deregulation of placental functions. Comparison of PS and AS indicated that ETS exposure and active smoking in pregnancy partly employ the same molecular mechanisms.
Publication Title
Deregulation of gene expression induced by environmental tobacco smoke exposure in pregnancy.
Sample Metadata Fields
Age
View Samples