Normal erythropoiesis requires a critical balance between proapoptotic and antipaoptotic pathways. Bcl-xl, an antiapoptotic protein is induced at end-stages of differentiation of erythroid precursors in response to erythropoietin. The details of the proapoptotic pathway and the critical proapoptotic proteins inhibited by Bcl-xl in erythropoiesis are not well understood. We employed gene targeting to ablate Nix, a proapoptotic BH3-domain only Bcl2 family protein, which is known to be transcriptionally induced during erythropoiesis. Nix null mice exhibited reticulocytosis and thrombocytosis in the peripheral blood; and profound splenomegaly with erythroblastosis in the spleen and bone marrow despite normal erythropoietin levels and blood oxygen tension. In vivo apoptosis was diminished in erythroblast precursors from Nix null spleens. To define the molecular consequences of Nix ablation on apoptosis and erythropoiesis, we conducted a detailed comparative analysis of gene expression in spleens from 8 week old Nix null mice and wild type controls. Of 45,101 genes analyzed, 514 were significantly upregulated and 386 down-regulated in Nix-/- splenocytes. Functional cluster analysis delineated the ten most highly regulated gene sets, revealing increased levels of cell cycle and erythroid genes, with decreased levels of cell death and B-cell genes.
Unrestrained erythroblast development in Nix-/- mice reveals a mechanism for apoptotic modulation of erythropoiesis.
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View SamplesAnalysis of a SigX knockout mutant of Pseudomonas aeruginosa H103 strain in minimal medium with glucose as carbon source (M9G).
The extra-cytoplasmic function sigma factor sigX modulates biofilm and virulence-related properties in Pseudomonas aeruginosa.
No sample metadata fields
View SamplesPreeclampsia (PE) is a complex, heterogeneous disorder of pregnancy, demonstrating considerable variability in observed maternal symptoms and fetal outcomes. We recently identified five clusters of placentas within a large gene expression microarray dataset (N=330, GSE75010), of which four contained a substantial number of PE samples. However, while transcriptional analysis of placentas can subtype patients, we hypothesized that the addition of epigenetic information should reveal gene regulatory mechanisms behind the distinct PE pathologies. We, therefore, subjected 48 of our samples to Infinium Human Methylation 450K arrays and investigated relationships between the gene expression and DNA methylation data.
Epigenetic regulation of placental gene expression in transcriptional subtypes of preeclampsia.
Sex, Specimen part, Disease
View SamplesPreeclampsia (PE) is a complex, heterogeneous disorder of pregnancy, demonstrating considerable variability in observed maternal symptoms and fetal outcomes. We hypothesized that this heterogeneity is due to the existence of multiple molecular forms of PE. To address our hypothesis, we created a large (N=330) human placental microarray data set consisting of seven previously published studies (GSE30186, GSE10588, GSE24129, GSE25906, GSE43942, GSE4707, and GSE44711) and 157 highly annotated samples from a BioBank (below).
Unsupervised Placental Gene Expression Profiling Identifies Clinically Relevant Subclasses of Human Preeclampsia.
Specimen part, Disease
View SamplesFetal growth restriction (FGR) is a heterogeneous disorder of pregnancy associated with pathologically low fetal and neonatal weights. We hypothesized that FGR consists of multiple placental subtypes, similar to what we have observed in preeclampsia. To address this hypothesis, we assembled a fetal growth-focused human placental microarray data set (N=97) consisting of 20 new normotensive suspected FGR samples (below), in addition to term controls (N=26) and hypertensive suspected FGR samples (N=51) from GSE75010.
Placental transcriptional and histologic subtypes of normotensive fetal growth restriction are comparable to preeclampsia.
Specimen part
View SamplesWistar rats, purchased from BRL (Fullinsdorf/BL, Switzerland), and WBN/Kob rats, purchased from SLC Inc. (Shizuoka, Japan), were specific pathogen-free. Rats were housed in groups of maximally 4 instandard cages (1,820 cm2 bottom area) and kept in our animal facility for various time periods between 1 week and 36 weeks (free access to standard rat chow and water; specific pathogen-free conditions; 20 degree C; day/night cycle simulated by artificial lighting of 50 lx from 7 a.m. to 7 p.m., dimmed in the remaining hours to almost complete darkness; air humidity 50 to 60%). Prior to surgery or sacrifice, the rats were fasted overnight (16 to18 h) with free access to water. All manipulations conformed with the Swiss Federal Guidelines on Animal Experiments and were approved by the local ethics committee.
Inflammation-dependent expression of SPARC during development of chronic pancreatitis in WBN/Kob rats and a microarray gene expression analysis.
Sex, Age, Specimen part, Time
View SamplesObjective:
Gene expression analysis in absence epilepsy using a monozygotic twin design.
Sex
View SamplesIntestinal macrophages rely on the constant replenishment by bone marrow derived Ly6Chigh monocytes in the adult organism. The developmental path from monocytes towards intestinal macrophages locally in the tissue is defined by the loss of Ly6C and acquisition of MHCII and CX3CR1 expression. We used microarray analysis to further characterise this local differentiation process.
Tissue-specific differentiation of colonic macrophages requires TGFβ receptor-mediated signaling.
Sex, Specimen part
View SamplesGene expression was studied from the blood derived RNAs of the Finnish family members as well as from 10 controls using GeneChip Human Genome U133 Plus2 (Affymetrix). Eight out of 10 family members in the expression analysis are heterozygous for the NPAT c.2437-2438delAG, three of which are NLPHL cases.
Exome sequencing reveals germline NPAT mutation as a candidate risk factor for Hodgkin lymphoma.
Specimen part, Disease, Disease stage, Subject
View SamplesCD103+CD11b+ dendritic cells (DC) are unique to the intestine, but the factors governing their differentiation are unclear. Here we show that transforming growth factor receptor 1 (TGF beta 1) has an indispensable, cell intrinsic role in the development of these cells. Deletion of Tgfbr1 results in markedly fewer intestinal CD103+CD11b+ DCs and a reciprocal increase in the CD103CD11b+ DC subset. Transcriptional profiling identifies markers that define the CD103+CD11b+ DC lineage, including CD101, TREM1 and Siglec-F, and shows that the absence of CD103+CD11b+ DCs in CD11c-Cre.Tgfbr1fl/fl mice reflects defective differentiation from CD103CD11b+ intermediaries, rather than an isolated loss of CD103 expression. The defect in CD103+CD11b+ DCs is accompanied by reduced generation of antigen-specific, inducible FoxP3+ regulatory T (Treg) cells in vitro and in vivo, and by reduced numbers of endogenous TH17 cells in the intestinal mucosa. Thus, TGF beta 1 mediated signalling may explain the tissue-specific development of these unique DCs.
TGFβR signalling controls CD103<sup>+</sup>CD11b<sup>+</sup> dendritic cell development in the intestine.
Specimen part
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