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Distinct signal transduction pathways downstream of the (P)RR revealed by microarray and ChIP-chip analyses.
Cell line
View SamplesWithin the overall project, we performed a set of microarray and chromatin-immunoprecipitation (ChIP)-chip experiments using siRNA against the (pro)renin receptor ((P)RR), stable overexpression of PLZF, the PLZF translocation inhibitor genistein and the specific V-ATPase inhibitor bafilomycin to dissect transcriptional pathways downstream of the (P)RR.
Distinct signal transduction pathways downstream of the (P)RR revealed by microarray and ChIP-chip analyses.
Cell line
View SamplesWithin the overall project, we performed a set of microarray and chromatin-immunoprecipitation (ChIP)-chip experiments using siRNA against the (pro)renin receptor ((P)RR), stable overexpression of PLZF, the PLZF translocation inhibitor genistein and the specific V-ATPase inhibitor bafilomycin to dissect transcriptional pathways downstream of the (P)RR.
Distinct signal transduction pathways downstream of the (P)RR revealed by microarray and ChIP-chip analyses.
Cell line
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 SamplesPreconditioning with a small dose of endotoxin confers unparalleled protection against otherwise lethal models of sepsis. The mechanisms of preconditioning have been investigated extensively in isolated immune cells such as macrophages. However, the role of tissue in mediating the protective response to preconditioning remains unknown. Using the kidney as a model organ, we identify the essential role of the renal epithelial cell in mediating the full expression of protective preconditioning. The protective phenotype is characterized by the clustering of macrophages around S1 segments of proximal tubules, which forms a functional unit mediating protection. To investigate the molecular pathways, we laser microdissected S1 segments from the following: 1) Non-preconditioned mice subjected to single-dose 5 mg/kg lipopolysaccharide (0111:B4, LPS) intraperitoneally for 24 hours. 2) Preconditioned mice subjected to 0.25 mg/kg LPS followed 24 hour later by 5 mg/kg LPS (LPS/LPS). 3) Control mice (saline vehicle).
Endotoxin Preconditioning Reprograms S1 Tubules and Macrophages to Protect the Kidney.
Sex, Specimen part, Treatment, Time
View SamplesThe 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
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