C.pn potentiated hyperlipidemia-induced inflammasome activity in cultured macrophages and in foam cells in atherosclerotic lesions of Ldlr/ mice. We discovered that C.pn-induced extracellular IL-1 triggers a negative feedback loop to inhibit GPR109a and ABCA1 expression and cholesterol efflux leading to accumulation of intracellular cholesterol and foam cell formation. Gpr109a and Abca1 were both upregulated in plaque lesions in Nlrp3/ mice in both hyperlipidemic and C.pn infection models.
Chlamydia pneumoniae Hijacks a Host Autoregulatory IL-1β Loop to Drive Foam Cell Formation and Accelerate Atherosclerosis.
Specimen part, Treatment
View SamplesEpithelial/mesenchymal transition (EMT) is associated with loss of cell adhesion molecules, such as E-cadherin, and increased invasion, migration, and proliferation in epithelial cancers. In non-small cell lung cancer (NSCLC), EMT is associated with greater resistance to EGFR inhibitors. However, its potential to predict response to other targeted drugs or chemotherapy has not been well characterized. The goal of this study was to develop a robust, platform-independent EMT gene expression signature and to investigate the association of EMT and drug response in NSCLC.
An epithelial-mesenchymal transition gene signature predicts resistance to EGFR and PI3K inhibitors and identifies Axl as a therapeutic target for overcoming EGFR inhibitor resistance.
Sex, Disease, Treatment, Race
View SamplesPurpose: Parturition is delayed by approximately 12 hours in transgenic mice expressing human corticotropin-releasing hormone (CRH) in placenta. The goal of the study was to identify the pathways in reproductive tissues (uterus and placenta) altered by placental expression of human CRH. Methods: Human BAC RP11-366K18 (CHORI) containing human CRH and cis-regulatory region was inserted into the mouse genome by microinjection and random integration to create the BAC1 line. The CRISPR/Cas9 system was used to delete a CRH regulatory element from the BAC1 line to create the CR1 line, eliminating expression of CRH in placenta. Total expression of uterus and placenta by RNA-seq at embryonic day 18.5 were compared between BAC1, CR1, and nontransgenic mice. Results: Genes known to be associated with luteolysis and initiation of parturition (Cav1, Gja1, Oxtr, Ptgs1, Ptgs2) were not differentially expressed in uterus of this model. Conclusions: CRH-mediated delay of parturition is likely independent of luteolysis. Overall design: mRNA-seq was performed on uterus and placenta harvested at embryonic day 18.5 from nontransgenic mice, Tg(BAC1) mice, and Tg(CR1) mice.
Anthropoid primate-specific retroviral element THE1B controls expression of CRH in placenta and alters gestation length.
Cell line, Subject
View SamplesCell proliferation is essential to rapid tissue growth and repair, but is inherently associated with considerable genome damage that cells must efficiently prevent or fix to prevent cell cycle arrest. Here, we implicate the transcription factor Gata6 in regulation of adult mouse hair follicle regeneration where it controls the renewal of the rapidly proliferating epithelial (matrix) progenitors and hence the extent of production of terminally differentiated lineages. We find that Gata6 protects against DNA damage associated with proliferation, thus preventing cell cycle arrest and apoptosis. Furthermore, we show that Gata6 stimulates the Eddarad/NF-kB pathway, important for DNA-damage repair and stress response in general, and for hair follicle growth in particular. Finally, we find Edaradd essential, downstream of Gata6 for cell survival and proliferation. Our data add to recent evidence in embryonic stem and neural progenitor cells, suggesting a model whereby developmentally regulated transcription factors protect from DNA damage associated with proliferation occurring at key stages of rapid tissue growth. Our data may aid in understanding why Gata6 is a frequent target of amplification in cancers. Overall design: Gene expression profiling by mRNA-seq to identify differentially expressed genes in wild type (WT) and Gata6 induced knockout (iKO) mouse epidermal keratinocytes
Gata6 promotes hair follicle progenitor cell renewal by genome maintenance during proliferation.
Treatment, Subject
View SamplesMetal oxide engineered nanoparticles, which are widely used in diverse applications, are known to impact terrestrial plants. These nanoparticles have a potential to induce changes in plant tissue transcriptomes, and thereby the productivity. Here we looked at how the two commonly used nanoparticles, nano-titania (TiO2) and nano-ceria (CeO2) can impact the underlying mechanisms associated plant growth at genome level.
Molecular and physiological responses to titanium dioxide and cerium oxide nanoparticles in Arabidopsis.
Age, Specimen part
View SamplesSeed germination of a terrestrial plant constitute dynamic changes in various physiological processes related to growth and development. These physiological processes can be affected by various abiotic and biotic stressors. Here we looked at how the two commonly used nanoparticles, nano-titania (TiO2) and nano-ceria (CeO2) can impact the underlying mechanisms associated with germination at genome level.
Phenotypic and genomic responses to titanium dioxide and cerium oxide nanoparticles in Arabidopsis germinants.
Age, Specimen part, Treatment
View SamplesIn homeostasis of adult vertebrate tissues, stem cells are thought to self-renew by infrequent and asymmetric divisions that generate another stem cell daughter and a progenitor daughter cell committed to differentiate. This model is based largely on in vivo invertebrate or in vitro mammal studies. Here we examine the dynamic behaviour of adult hair follicle stem cells in their normal setting by employing mice with repressible H2B-GFP expression to track cell divisions and Cre inducible mice to perform long-term single cell lineage tracing. We provide direct evidence for the infrequent stem cell division model in intact tissue. Moreover, we find that differentiation of progenitor cells occurs at different times and tissue locations than self-renewal of stem cells. Distinct fates of differentiation or self-renewal are assigned to individual cells in a temporal-spatial manner. We propose that large clusters of tissue stem cells behave as populations, whose maintenance involves unidirectional daughter-cell fate decisions.
Distinct self-renewal and differentiation phases in the niche of infrequently dividing hair follicle stem cells.
Specimen part
View SamplesTransgenic rice plants expressing isopentenyltransferase (IPT), an enzyme that catalyzes the rate-limiting step in CK synthesis under the control of SARK, a maturation- and stress-inducible promoter. Increased CK production resulted in sink source alteration and enhanced drought tolerance of the transgenic plants.
Cytokinin-mediated source/sink modifications improve drought tolerance and increase grain yield in rice under water-stress.
Age, Specimen part
View SamplesTime-course and concentration-effect experiments with multiple time points and drug concentrations provide far more valuable information than experiments with just two design-points (treated vs. control), as commonly performed in most microarray studies. Analysis of the data from such complex experiments, however, remains a challenge. Here we present a semi-automated method for fitting time profiles and concentration-effect patterns, simultaneously, to gene expression data. The submodels for time-course included exponential increase and decrease models with parameters such as initial expression level, maximum effect, and rate-constant (or half-time). The submodel for concentration-effect was a 4-parameter Hill model.
Simultaneous modeling of concentration-effect and time-course patterns in gene expression data from microarrays.
No sample metadata fields
View SamplesQuiescent hair follicle (HF) bulge stem cells (SCs) differentiate to early progenitor (EP) hair germ (HG) cells, which divide to produce transit-amplifying (TA) matrix cells. EPs can revert to SCs upon injury, but whether this de-differentiation occurs in normal HF homeostasis (hair cycle), and the mechanisms regulating both differentiation and de-differentiation are unclear. Here we use lineage tracing, gain of function, transcriptional profiling, and functional assays to examine the role of observed endogenous Runx1 level changes in the hair cycle. We find that forced Runx1 expression implements hair degeneration (catagen) and simultaneously promotes changes in the quiescent bulge SC transcriptome towards a cell-state resembling the EP HG fate. This cell-state transition is functionally reversible. We propose that SC differentiation and de-differentiation are likely to occur during normal HF degeneration and niche restructuring in response to changes in endogenous Runx1 levels associated with SC location with respect to the niche.
High Runx1 levels promote a reversible, more-differentiated cell state in hair-follicle stem cells during quiescence.
Specimen part
View Samples