To identify genes dysregulated in bipolar disorder (BD1) we carried out global gene expression profiling using whole-genome microarrays. To minimize genetic variation in gene expression levels between cases and controls we compared expression profiles in lymphoblastoid cell lines from monozygotic twin pairs discordant for the disease. We identified 82 genes that were differentially expressed by 1.3-fold in 3 BD1 cases compared to their co-twins, and which were statistically (p 0.05) differentially expressed between the groups of BD1 cases and controls. Using qRT-PCR we confirmed the differential expression of some of these genes, including: KCNK1, MAL, PFN2, TCF7, PGK1, and PI4KCB, in at least 2 of the twin pairs. In contrast to the findings of a previous study by Kakiuchi and colleagues with similar discordant BD1 twin design1 our data do not support the dysregulation of XBP1 and HSPA5. From pathway and gene ontology analysis we identified up-regulation of the WNT signalling pathway and the biological process of apoptosis. The differentially regulated genes and pathways identified in this study may provide insights into the biology of BD1.
Expression profiling in monozygotic twins discordant for bipolar disorder reveals dysregulation of the WNT signalling pathway.
Sex
View SamplesRecent advances in high density oligonucleotides microarray technology have brought solutions for molecular profiling of human samples at an unprecedented resolution. We mapped whole blood RNA from healthy volunteers and CD34+ from cytapheresis to Human Exon ST 1.0 microarrays. We compared mature blood cells samples with immature CD34+ samples and each of these compartiement with a broad panel of solid tissues. By scanning the expression of over one million known or predicted exons, transcripts such as INPP4B, NEDD9 CD74 and VAV3 were identified as alternatively transcribed between haematopoietic system and solid tissues. The very large combinatorial complexity conveyed by alternative splicing contributes to the specific functional properties of blood cells and haematopoietic stem cells. The gene expression profiles are freely accessible through a dynamic web atlas, providing to the medical and scientific community a simple mean to interrogate and visualize this reference dataset. Finally, the relevance and the precision provided by this exon expression map suggest that exon arrays may be a powerful tool to link specific peripheral whole blood exon signatures modifications to many diseases such as cancer or auto-immune disorders.
Expression map of the human exome in CD34+ cells and blood cells: increased alternative splicing in cell motility and immune response genes.
Specimen part
View SamplesThe first week of human pre-embryo development is characterized by the induction of totipotency and then pluripotency. The understanding of this delicate process will have far reaching implication for in vitro fertilization and regenerative medicine. Human mature MII oocytes and embryonic stem (ES) cells are both able to achieve the feat of cell reprogramming towards pluripotency, either by somatic cell nuclear transfer or by cell fusion, respectively. Comparison of the transcriptome of these two cell types may highlight genes that are involved in pluripotency initiation. Therefore, based on a microarray compendium of 205 samples, produced in our laboratory or from public databases, we compared the gene expression profile of mature MII oocytes and human ES cells (hESC) to that of somatic tissues. We identified a common oocyte/hESC gene expression profile, which included a strong cell cycle signature, a large chromatin remodelling network (TOP2A, DNMT3B, JARID2, SMARCA5, CBX1, CBX5) and 18 different zinc finger transcription factors, including ZNF84. Strikingly, a large set of genes was found to code for proteins involved in the ubiquitination and proteasome pathway. Upon hESC differentiation into embryoid bodies, the transcription of this pathway declines. In vitro, we observed a selective sensitivity of hESC to the inhibition of the activity of the proteasome, resulting in loss of pluripotency and cell growth at doses without any detectable effects on differentiated cells. Taken together, these results suggest that the proteasome pathway may play a role in initiating and maintaining pluripotency during early development and in hESC.
A gene expression signature shared by human mature oocytes and embryonic stem cells.
No sample metadata fields
View SamplesPluripotent stem cells, which are capable to generate any cell type of the human body, such as human embryonic stem cells (hESC) or human induced pluripotent stem cells (hiPS) are a very promising source of cells for regenerative medicine. However, the genesis, the in vitro amplification and the differentiation of these cells still need improvement before clinical use. This study aimed to improve our knowledge on these critical steps in pluripotent stem cell generation. We derived new hESC lines, generated hiPS and compared these cell types with human foreskin fibroblasts and partially reprogrammed fibroblasts.
A gene expression signature shared by human mature oocytes and embryonic stem cells.
Specimen part, Cell line
View SamplesFormation of blood vessels requires the concerted regulation of an unknown number of genes in a spatial-, time- and dosage-dependent manner. We investigated vascular development in vivo by determining global gene regulation throughout the formation of the chick chorio-allantoic membrane (CAM). Our study provides a comprehensive molecular map of vascular maturation during developmental angiogenesis and might thus be a valuable resource to streamline further research of candidates susceptible to mediate pathological angiogenesis.
Correlating global gene regulation to angiogenesis in the developing chick extra-embryonic vascular system.
No sample metadata fields
View SamplesWe have used an integrative high content analysis approach to identify the specific miRNAs implicated in EGF signaling in HeLa cells as potential mediators of cancer mediated functions. We have used microarray and deep-sequencing technologies in order to obtain a global view of the EGF miRNA transcriptome with a robust experimental cross-validation. By applying a procedure based on Rankprod tests, we have delimited a solid set of EGF-regulated miRNAs. After validating regulated miRNAs by RT-qPCR, we have derived protein networks and biological functions from the predicted targets of the regulated miRNAs to gain insight into the potential role of miRNAs in EGF-treated cells. In addition, we have analyzed sequence heterogeneity due to editing relative to the reference sequence (isomirs) among regulated miRNAs. Overall design: Time course experiment comparing HeLa gene expression in response to EGF analyzed by small RNA-seq using Illumina 36-bp read massively parallel sequencing. Three independent experiments were performed where HeLa cells were serum deprived for 24 hours and were either left untreated or treated with EGF for 6h and harvested for RNA extraction. Thus, a total of 6 samples were analyzed, 3 controls and the 3 respective treated counterparts. These same samples were also analyzed in parallel on two different microarray platforms.
Microarray and deep sequencing cross-platform analysis of the mirRNome and isomiR variation in response to epidermal growth factor.
Cell line, Subject
View SamplesBrain gene expression profiling studies of suicide and depression using oligonucleotide microarrays have often failed to distinguish these two phenotypes. Moreover, next generation sequencing approaches are more accurate in quantifying gene expression and can detect alternative splicing. Using RNA-seq, we examined whole-exome gene and exon expression in non-psychiatric controls (CON, N=29), DSM-IV major depressive disorder suicides (MDD-S, N=21) and MDD non-suicides (MDD, N=9) in the dorsal lateral prefrontal cortex (Brodmann Area 9) of sudden death medication-free individuals post mortem. Using small RNA-seq, we also examined miRNA expression (nine samples per group). DeSeq2 identified 35 genes differentially expressed between groups and surviving adjustment for false discovery rate (adjusted P<0.1). In depression, altered genes include humanin-like-8 (MTRNRL8), interleukin-8 (IL8), and serpin peptidase inhibitor, clade H (SERPINH1) and chemokine ligand 4 (CCL4), while exploratory gene ontology (GO) analyses revealed lower expression of immune-related pathways such as chemokine receptor activity, chemotaxis and cytokine biosynthesis, and angiogenesis and vascular development in (adjusted P<0.1). Hypothesis-driven GO analysis suggests lower expression of genes involved in oligodendrocyte differentiation, regulation of glutamatergic neurotransmission, and oxytocin receptor expression in both suicide and depression, and provisional evidence for altered DNA-dependent ATPase expression in suicide only. DEXSEq analysis identified differential exon usage in ATPase, class II, type 9B (adjusted P<0.1) in depression. Differences in miRNA expression or structural gene variants were not detected. Results lend further support for models in which deficits in microglial, endothelial (blood-brain barrier), ATPase activity and astrocytic cell functions contribute to MDD and suicide, and identify putative pathways and mechanisms for further study in these disorder Overall design: We examined whole-exome gene and exon expression in non-psychiatric controls (CON, N=29), DSM-IV major depressive disorder suicides (MDD-S, N=21) and MDD non-suicides (MDD, N=9) in the dorsal lateral prefrontal cortex (Brodmann Area 9) of sudden death medication-free individuals post mortem. Using small RNA-seq, we also examined miRNA expression (nine samples per group).
Whole-transcriptome brain expression and exon-usage profiling in major depression and suicide: evidence for altered glial, endothelial and ATPase activity.
No sample metadata fields
View SamplesNotch signaling is widely implicated in mouse mammary gland development and tumorigenesis. To investigate the effects of acute activation of Notch signaling in the mammary epithelial compartment, we generated bi-transgenic MMTV-rtTA; TetO-NICD1 (MTB/TICNX) mice that conditionally express a constitutively active NOTCH1 intracellular domain (NICD1) construct in the mammary epithelium upon doxycycline administration.
Notch promotes recurrence of dormant tumor cells following HER2/neu-targeted therapy.
Sex, Age, Specimen part, Treatment, Time
View SamplesCryptosporidium hominis and parvum primarily infect intestinal epithelial cells, which, in turn, play a key role in activating and communicating with the host immune system. To determinate which genes are regulated during early infection of non-transformed human epithelial cells, human ileal mucosa was removed (from surgical specimens), placed on collagen membranes, and cultured as explants. Explant cultures were infected with C. parvum, C. hominis, or control culture medium. After 24 hrs, RNA was extracted and analyzed using Affmetrix GeneChip microarrays. Among the more prominent genes with regulated expression was Osteoprotegerin (OPG), which was increased in all of the explants at 24 hrs and further up-regulated 1.58 fold by C. parvum and 2.54 fold by C. hominis infection compared with uninfected explants. Using real time PCR, we confirmed a 3.14 and 3.79 fold increase in OPG mRNA after infection with C. parvum and C. hominis respectively.
Cryptosporidium infection of human intestinal epithelial cells increases expression of osteoprotegerin: a novel mechanism for evasion of host defenses.
No sample metadata fields
View SamplesVitis vinifera endogenous small RNAs Overall design: Size fractionated small RNA from total RNA extracts of Vitis vinifera leaves, inflorescences, tendrils and small berries were ligated to adapters, purified again and reverse transcribed. After PCR amplification the sample was subjected to Solexa/Illumina high throughput pyrosequencing. Please see www.illumina.com for details of the sequencing technology.
Identification of grapevine microRNAs and their targets using high-throughput sequencing and degradome analysis.
Specimen part, Subject
View Samples