Whole-transcriptome survey of gene expression differences between germ-free (GF) and conventionally raised (CONV-R) mice.
The gut microbiota modulates host amino acid and glutathione metabolism in mice.
Specimen part
View SamplesWe hypothesized altered expression of Proteases in calls capable of physiological invasion vs angiogenesis. We analyzed trophoblasts isolated from first trimester placenta that are invasive, and placental endothelial cells, that gave a high angiogenic potential. We found different expression levels of most proteases.
Different Preference of Degradome in Invasion versus Angiogenesis.
Specimen part
View SamplesWe hypothesized that the trophoblast secretes anti-angiogenic factors, which increase in late pregnancy to limit angiogenesis. Therefore, we determined the paracrine effect of primary human trophoblasts from early versus late pregnancy on the angiogenic potential of isolated feto-placental endothelial cells.
Pigment epithelium-derived factor (PEDF): a novel trophoblast-derived factor limiting feto-placental angiogenesis in late pregnancy.
Specimen part
View SamplesBRD4 assembles transcriptional machinery at gene super-enhancer regions and governs the expression of genes that are critical for cancer progression. However, it remains unclear whether BRD4-mediated gene transcription is required for tumor cells to develop drug resistance. Our data show that prolonged treatment of luminal breast cancer cells with AKT inhibitors induces FOXO3a de-phosphorylation, nuclear translocation, and disrupts its association with SIRT6, eventually leading to FOXO3a acetylation as well as BRD4 recognition. Acetylated FOXO3a recognizes the BD2 domain of BRD4, recruits the BRD4/RNAPII complex to the CDK6 gene promoter and induces its transcription. Pharmacological inhibition of either BRD4/FOXO3a association or CDK6 significantly overcomes the resistance of luminal breast cancer cells to AKT inhibitors in vitro and in vivo. Our study reports the involvement of BRD4/FOXO3a/CDK6 axis in AKTi resistance and provides potential therapeutic strategies for treating resistant breast cancer. Overall design: Total RNA was extracted from MK2206 resistant cells for RNA sequencing. Parental cells without MK2206 resistance were used as controls.
Targeting the BRD4/FOXO3a/CDK6 axis sensitizes AKT inhibition in luminal breast cancer.
Specimen part, Cell line, Subject
View SamplesDespite significant advances in our understanding of the biology determining systemic energy homeostasis, the treatment of obesity remains a medical challenge. Activation of AMP-activated protein kinase (AMPK) has been proposed as an attractive strategy for the treatment of obesity and its complications. AMPK is a conserved, ubiquitously expressed, heterotrimeric serine/threonine kinase whose short-term activation has multiple beneficial metabolic effects. Whether these translate into long-term benefits for obesity and its complications is unknown. Here, we observe that mice with chronic AMPK activation, resulting from mutation of the AMPK ?2 subunit, exhibit ghrelin signalling-dependent hyperphagia, obesity and impaired pancreatic islet insulin secretion. Humans bearing the homologous mutation manifest a congruent phenotype. Our studies highlight that long-term AMPK activation can have adverse metabolic consequences with implications for pharmacological strategies seeking to chronically activate AMPK systemically to treat metabolic disease. Overall design: Transcriptomic profiling of the hypothalamic arcuate nucleus from AMPK ?2 R299Q knock-in mice
Chronic Activation of γ2 AMPK Induces Obesity and Reduces β Cell Function.
Specimen part, Cell line, Subject
View SamplesGenome-wide alternative splice analysis of RNA from lupus and its severe form lupus nephritis
Genome-wide peripheral blood transcriptome analysis of Arab female lupus and lupus nephritis.
Sex, Specimen part, Disease stage
View SamplesWe performed single-cell mRNA-Seq on wild-type mouse keratinocytes co-cultured with keratinocytes in which beta-catenin was activated. We identified seven distinct cell states in cultures that had not been exposed to the beta-catenin stimulus. Using temporal single-cell analysis we reconstruct the cell fate changes induced by neighbor Wnt activation. Gene expression heterogeneity was reduced in neighboring cells and this effect was most dramatic for protein synthesis associated genes. The changes in gene expression were accompanied by a shift from a quiescent to a more proliferative stem cell state. By integrating imaging and reconstructed sequential gene expression changes during the state transition we identified transcription factors, including Smad4 and Bcl3, that were responsible for effecting the transition in a contact-dependent manner. Our data indicate that non cell autonomous Wnt/beta-catenin signaling decreases transcriptional heterogeneity and further our understanding of how epidermal Wnt signaling orchestrates regeneration and self-renewal. Overall design: Comparison of cells exposed to Wnt activated neighbors versus unactivated.
Epidermal Wnt signalling regulates transcriptome heterogeneity and proliferative fate in neighbouring cells.
Specimen part, Treatment, Subject
View SamplesAirway epithelial cells (AEC) are critical components of the inflammatory and immune response during exposure to pathogens. AECs in monolayer culture and differentiated epithelial cells in air-liquid interface (ALI) represent two distinct and commonly used in vitro models, yet differences in their response to pathogens have not been investigated. In this study, we compared the transcriptional effects of flagellin on AECs in monolayer culture versus ALI culture using exon microarrays and RNAsequencing. We found that AECs cultured in monolayer and ALI have strikingly different transcriptional states at baseline. When challenged with flagellin, monolayer AEC cultures greatly increased transcription of numerous genes mapping to wounding response, immunity and inflammatory response. In contrast, AECs in ALI culture had an unexpectedly muted response to flagellin, both in number of genes expressed and relative enrichment of inflammatory and immune pathways. In conclusion, In vitro culturing methods have a dramatic effect on the transcriptional profile of AECs at baseline and after stimulation with flagellin. These differences suggest that epithelial responses to pathogen challenges are distinctly different in culture models of intact and injured epithelium. Overall design: A total of eight independent RNAseq experiments were conducted. Four RNAseq experiments (n = 2 unstimulated, n = 2 stimulated with flagellin) were performed using AECs grown in monolayer. Four RNAseq experiments (n =2 unstimulated, n = 2 stimulated with flagellin) were conducted using AECs grown in ALI cultures
Plasticity of airway epithelial cell transcriptome in response to flagellin.
No sample metadata fields
View SamplesRationale: Obstructive sleep apnea (OSA) has been associated with metabolic dysregulation and systemic inflammation. This may be due to pathophysiologic effects of OSA on visceral adipose tissue. We sought to assess the transcriptional consequences of OSA on adipocytes by utilizing pathway-focused analyses.
A pathway-based analysis on the effects of obstructive sleep apnea in modulating visceral fat transcriptome.
Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Plasticity of airway epithelial cell transcriptome in response to flagellin.
Specimen part, Treatment
View Samples