Preeclampsia (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 SamplesThis data set was generated by the UK Brain Expression Consortium and consists of gene expression data generated from post-mortem human brain samples, dissected from 10 brain regions and originating from a large cohort of neurologically and neuropathologically normal individuals.
Analysis of gene expression data using a linear mixed model/finite mixture model approach: application to regional differences in the human brain.
Sex, Disease, Subject
View SamplesThe placental microvasculature of the human fetus is essential for the efficient transfer of gases, nutrients and waste between the mother and fetus. Microvascular hypoplasia of the terminal villi is associated with the placental pathology observed in cases of severe Intra Uterine Growth Restriction (IUGR). We used novel methods to isolate a pure population of placental microvascular endothelial cells from control preterm placentas (n=3) and placenta complicated by severe IUGR (n=6) with superimposed preeclampsia (n=5). Distal placental villous tissue was collected to enrich for terminal villi. Tissue was minced, digested and placental microvascular endothelial cells (PlMEC) were positively selected using tocosylated magnetic Dynabeads labeled with Human Endothelial Antigen lectin. The purity of the PlMEC (95%) was assessed by CD31 immunocytochemistry. RNA was extracted from the PlMEC samples and also from 3 term placenta and subjected to Affymetrix microarray analysis (U133Plus2 array chips). Data from the 3 term placentas and 3 preterm PlMEC arrays was used to generate an endothelial cell specific gene profile. This profile was used to identify the endothelial genes differentially regulated in all 6 IUGR cases. BTNL9 and NTRK2 transcripts were upregulated and SAA1, GNAS and SLAMF1 transcripts were downregulated as relative to the preterm controls. These changes were validated by Real time PCR in the PlMEC samples. This novel study is the first to identify endothelial candidate genes that may play a role in the villous hypoplasia of severe IUGR. This work advances our understanding of the molecular defects in placental microvascular endothelial cells in normal and pathologic pregnancies.
A distinct microvascular endothelial gene expression profile in severe IUGR placentas.
Sex
View SamplesMajor- and minor-group rhinoviruses enter their host by binding to the cell surface molecules ICAM-1 and LDL-R, respectively, which are present on both macrophages and epithelial cells. Although epithelial cells are the primary site of productive HRV infection, previous studies have implicated macrophages in establishing the cytokine dysregulation that occurs during rhinovirus-induced asthma exacerbations. Even though major- and minor-group rhinoviruses are nearly genetically identical, these viruses do not replicate with equal success in monocyte-lineage cell lines. In human primary macrophages, differential mitochondrial activity and signaling pathway activation was observed between major- and minor-group rhinovirus upon initial HRV binding, indicating discordant receptor-dependent response to these rhinovirus types. As well, variances in phosphorylation of kinases (p38, JNK, ERK5) and transcription factors (ATF-2, CREB, CEBP-alpha) were observed between the major- and minor- group HRV treatments. The difference between major- and minor- group HRV activation of signaling pathways was confirmed through RNA-sequencing and observation of differential production of the asthma-relevant cytokines CCL20, CCL2, and IL-10. This is the first report of genetically similar viruses eliciting dissimilar cytokine release, transcription factor phosphorylation, and MAPK activation from macrophages. These results suggest that receptor dependence plays a role in establishing the inflammatory microenvironment initiated in part by monocytic-lineage cells in the human airway upon exposure to rhinovirus. Overall design: RNA sequencing of monocyte-derived macrophages after mock infection or infection by HRV16 or HRV1A
Major and minor group rhinoviruses elicit differential signaling and cytokine responses as a function of receptor-mediated signal transduction.
No sample metadata fields
View SamplesAlphaviruses establish a persistent infection in arthropod vectors, which is essential for effective transmission of the virus to vertebrate hosts. The development of persistence in insects is not well understood, although it is thought to involve the innate immune response. Using a transgenic fly system (SINrep) expressing a self-replicating viral genome, we have previously demonstrated the antiviral response of the Drosophila Imd (Immune Deficiency) and Jak-STAT innate immunity pathways.
An antiviral role for antimicrobial peptides during the arthropod response to alphavirus replication.
Specimen part
View SamplesPolycomb repressive complex 2 (PRC2-EZH2) methylates histone H3 at lysine 27 (H3K27) and is required to maintain gene repression during development. Misregulation of PRC2 is linked to a range of neoplastic malignancies, which is believed to involve methylation of H3K27. However, the full spectrum of non-histone substrates of PRC2 that might also contribute to PRC2 function is not known. We characterized the target recognition specificity of PRC2 and used the resultant data to screen for novel potential targets. The RNA polymerase II (Pol II) transcription factor, Elongin A (EloA), is methylated by PRC2 in vivo. Mutation of the methylated EloA residue decreased repression of many, but not all, PRC2 target genes as measured by both steady state and nascent RNA levels. We propose that PRC2 regulates transcription of a subset of target genes in part via methylation of EloA. Overall design: We examined the transcripitonal profile of EEDnull, EloAnull, EloA mutant, and parental mouse embryonic stem cells by RNAseq. Please note that the .bw processed data file was generated from the *mESC replicate samples together and linked to the corresponding *rep1 sample records.
Polycomb Repressive Complex 2 Methylates Elongin A to Regulate Transcription.
Specimen part, Subject
View SamplesPolycomb repressive complex 2 (PRC2-EZH2) methylates histone H3 at lysine 27 (H3K27) and is required to maintain gene repression during development. Misregulation of PRC2 is linked to a range of neoplastic malignancies, which is believed to involve methylation of H3K27. However, the full spectrum of non-histone substrates of PRC2 that might also contribute to PRC2 function is not known. We characterized the target recognition specificity of PRC2 and used the resultant data to screen for novel potential targets. The RNA polymerase II (Pol II) transcription factor, Elongin A (EloA), is methylated by PRC2 in vivo. Mutation of the methylated EloA residue decreased repression of many, but not all, PRC2 target genes as measured by both steady state and nascent RNA levels. We propose that PRC2 regulates transcription of a subset of target genes in part via methylation of EloA. Overall design: We examined the nascent transcripiton profile of mES cells by adding 5-Bromouridine (BrU) to the media for 10 min. Following RNA isolation, BrU-labelled nascent RNA species were affinity purified using BrdU antibody and sequenced after library preparation. Please note that each .bw file was generated from two replicate samples together and linked to the corresponding *rep1 sample records.
Polycomb Repressive Complex 2 Methylates Elongin A to Regulate Transcription.
Specimen part, Subject
View SamplesMost vertebrate organs are composed of epithelium surrounded by support and stromal tissues formed from mesenchyme cells, which are not generally thought to form organized progenitor pools. Here we use clonal cell labeling with multicolor reporters to characterize individual mesenchymal progenitors in the developing mouse lung. We observe a diversity of mesenchymal progenitor populations with different locations, movements, and lineage boundaries. Airway smooth muscle (ASM) progenitors map exclusively to mesenchyme ahead of budding airways. Progenitors recruited from these tip pools differentiate into ASM around airway stalks; flanking stalk mesenchyme can be induced to form an ASM niche by a lateral bud or by an airway tip plus focal Wnt signal. Thus, mesenchymal progenitors can be organized into localized and carefully controlled domains that rival epithelial progenitor niches in regulatory sophistication.
Mesenchymal cells. Defining a mesenchymal progenitor niche at single-cell resolution.
Specimen part, Treatment
View SamplesMaster regulatory genes require stable silencing by the Polycomb-Group (PcG) to prevent improper expression during differentiation and development. Some PcG proteins covalently modify histones, which contributes to heritable repression. The role for other effects on chromatin structure is less understood. We characterized the organization of PcG target genes in mouse ES cells and neural progenitors using high-resolution 5C technology and super-resolution microscopy. The genomic loci of repressed PcG target genes formed discrete, small domains of tight interaction that corresponded to locations bound by canonical Polycomb Repressive Complex 1 (PRC1). These domains changed during differentiation as PRC1 binding changed. Their formation depended upon the Polyhomeotic component of canonical PRC1, and occurred independently of PRC1-catalyzed ubiquitylation. PRC1 domains differ from topologically associating domains in numerous aspects . These domains have the potential to play a key role in transmitting epigenetic silencing of PcG targets by linking PRC1 to formation of a repressive higher order structure. Overall design: RNA-Seq was performed to compare gene expression of in vitro derived NPC and Phc1 knock-out mESC with wild type ESC. Experiments were performed in dupicates. 50base single end sequencing was performed on Illumina HiSeq2000. Reference genome is mm9.
Polycomb Repressive Complex 1 Generates Discrete Compacted Domains that Change during Differentiation.
Specimen part, Cell line, Subject
View SamplesWe profiled genome-wide accesssible chromatin data and RNA-seq from four species (zebrafish, stickleback, mouse, and human) to identify commonly regulated genes and regulatory metods in intestinal epithelial cells (IECs). We identify a group genes that are commonly expressed in IECs and genes that are commonly expressed along the length of the intestine in fish and mammals. Using accessible chromatin data we identified enriched transcription factor binding site motifs In IECs and sites that are commonly accessible in IECs in all species. Finally, we confirm the ability for these regions from multiple species to drive conserved expression in IECs using a zebrafish reporter assay. Overall design: Examination of expression levels and chromatin accessibility in intestinal epithelaial cells in zebrafish
Genomic dissection of conserved transcriptional regulation in intestinal epithelial cells.
No sample metadata fields
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