The ontogeny of human Langerhans cells (LCs) remains poorly characterized, in particular the nature of LC precursors and the factors that may drive LC differentiation. Through a systematic transcriptomic analysis of TSLP-activated dendritic cells (DCs), we unexpectedly identified markers that have been associated with a skin-homing potential as well as with a LC phenotype. We performed transcriptomic analysis of TSLP-activated blood DCs, as compared to freshly purified, Medium-, and TNF-activated DCs. Among TSLP up-regulated genes, we identified molecules associated with skin homing, LC phenotype, and LC function, as determined by a literature-based survey. Conversely, genes not expressed in LCs were not found among TSLP-induced genes. Further experiments showed that TGF- synergized with TSLP leading to the differentiation of blood BDCA-1+ DCs into bona fide Birbeck granule-positive LCs.
Human blood BDCA-1 dendritic cells differentiate into Langerhans-like cells with thymic stromal lymphopoietin and TGF-β.
Specimen part
View SamplesMicroarray studies revealed that as a first hit, SV40 T/t-antigen causes deregulation of 462 genes in mammary gland cells (ME-cells) of WAP-SVT/t transgenic animals. The majority of deregulated genes are cell-proliferation specific and Rb-E2F dependent, causing ME-cell proliferation and gland hyperplasia but not breast cancer formation. In the breast tumor cells, a further 207 genes are differentially expressed, most of them belonging to the cell communication category. In tissue culture, breast tumor cells frequently switch off WAP-SVT/t transgene expression and regain the morphology and growth characteristics of normal-ME-cells, although the tumor-revertant cells are aneuploid and only 114 genes regain the expression level of normal-ME-cells. The profile of retransformants shows that only 38 deregulated genes appear to be tumor-relevant and that none of them is considered to be a typical breast cancer gene.
Gene expression profiling: cell cycle deregulation and aneuploidy do not cause breast cancer formation in WAP-SVT/t transgenic animals.
No sample metadata fields
View SamplesDerivation and expansion of human umbilical cord blood-derived endothelial colony forming cells under serum-free conditions - a transcriptome analysis.
Optimization of the culturing conditions of human umbilical cord blood-derived endothelial colony-forming cells under xeno-free conditions applying a transcriptomic approach.
Specimen part
View SamplesIntegration of multiple signals shapes cell adaptation to their microenvironment through synergistic and antagonistic interactions. The combinatorial complexity governing signal integration for multiple cellular output responses has not been resolved. For outputs measured in the conditions 0 (control), signals X, Y, X+Y, combinatorial analysis revealed 82 possible interaction profiles, which we biologically assimilated to 5 positive, and 5 negative interaction modes. To experimentally validate their use in living cells, we designed an original computational workflow, and applied it to transcriptomics data of innate immune cells integrating physiopathological signal combinations. Up to 9 of the 10 defined modes coexisted in context-dependent proportions. Each integration mode was enriched in specific molecular pathways, suggesting a coupling between genes involved in particular functions, and the corresponding mode of integration. We propose that multimodality and functional coupling are general principles underlying the systems level integration of physiopathological and pharmacological stimuli by mammalian cells.
Combinatorial code governing cellular responses to complex stimuli.
Time
View SamplesEfforts to unravel the mechanisms underlying taste sensation (gustation) have largely focused on rodents. The first comprehensive database of gene expression in primate (Macaca fascicularis) taste buds is presented. This database provides a foundation for further studies in diverse aspects of taste biology. A taste bud gene expression database was generated using laser capture microdissection (LCM) of tissue freeze medium OTC embedded macaque tongue tissue blocks. We collected fungiform (FG) taste buds at the front of the tongue, circumvallate (CV) taste buds at the back of the tongue, as well as non-gustatory lingual epithelium (LE). Gene expression was also analyzed in the top and bottom portions of CV taste buds collected using LCM. Samples were collected from 10 animals - 7 female, 3 male.
Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes.
Sex, Age, Specimen part
View SamplesAnesthetic gases elicit organ protection in patients undergoing coronary artery bypass graft (CABG) surgery. This study aimed at identifying myocardial transcriptional phenotypes and anesthetic-induced changes in gene expression to predict cardiovascular biomarkers and cardiac function after off-pump CABG.
Gene regulatory control of myocardial energy metabolism predicts postoperative cardiac function in patients undergoing off-pump coronary artery bypass graft surgery: inhalational versus intravenous anesthetics.
No sample metadata fields
View SamplesMedulloblastoma (MB) is the most common malignant brain tumor in children, among whom overexpression or amplification of MYC oncogenes has been associated with poor clinical outcome. Although the MYC functions during normal development and oncogenesis in various systems have been extensively investigated, the transcriptional targets mediating MYC effects in MB are still elusive. Their identification and roles during MB onset and progression are important and will ultimately suggest novel potential therapeutic targets. cDNA microarray analysis was used to compare the effects of overexpressing and silencing MYC on the transcriptome of a MB-derived cell line. We identified 209 genes with potential relevance to MYC-dependent cellular responses in MB. Among the MYC-responsive genes, we found members of the bone morphogenetic protein (BMP) signaling pathway, which plays a crucial role during the development of the cerebellum. In particular, the cytokine gene BMP7 was identified as a direct target of MYC in MB cells. Similar to the effect induced by BMP7 silencing by siRNA, the use of a small-molecule inhibitor of the BMP/SMAD signaling pathway reduced cell viability in a panel of MB cells. Altogether, our findings indicate that high MYC levels drive BMP7 expression in MB to induce pro-survival and pro-proliferative cellular pathways. This observation suggests that targeting the BMP/SMAD pathway may be a new therapeutic concept for the treatment of childhood MB.
Bone morphogenetic protein-7 is a MYC target with prosurvival functions in childhood medulloblastoma.
Specimen part, Cell line
View SamplesRegulatory T cells (Treg) play a pivotal role in modulating immune responses and were shown to decrease atherosclerosis in murine models. How this effect is brought about remains elusive.
Depletion of FOXP3+ regulatory T cells promotes hypercholesterolemia and atherosclerosis.
Specimen part, Treatment
View SamplesIn response to viral pathogens, the host upregulates antiviral genes that suppress translation of viral mRNAs. However, induction of such antiviral responses may not be exclusive to viruses as the pathways lie at the intersection of broad inflammatory networks that can also be induced by bacterial pathogens. Using a model of Gram-negative sepsis, we show that propagation of kidney damage initiated by a bacterial origin ultimately involves antiviral responses that result in host translation shutdown. We determined that activation of the Eif2ak2-Eif2a axis is the key mediator of translation initiation block in late phase sepsis. Reversal of this axis mitigated kidney injury. Furthermore, temporal profiling of the kidney translatome revealed that multiple genes involved in formation of the initiation complex were translationally altered during bacterial sepsis. Collectively, our findings implicate that translation shutdown is indifferent to the specific initiating pathogen and is an important determinant of tissue injury in sepsis. Overall design: Bulk 20 um thickness specimens from cross-sectional human kidney biopsies embedded in OCT underwent RNA sequencing. All subjects had ATN, AIN, or a mix of both conditions.
Bacterial sepsis triggers an antiviral response that causes translation shutdown.
Sex, Age, Specimen part, Disease, Subject
View SamplesThe miR-17-92 microRNA cluster is often activated in cancer cells, but the identity of its targets remains largely elusive. Here we examined the effects of activation of the entire miR-17-92 cluster on global protein expression in neuroblastoma cells.
The miR-17-92 microRNA cluster regulates multiple components of the TGF-β pathway in neuroblastoma.
Specimen part
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