All-trans retinoic acid (tRA) is the bioactive derivative of vitamin A that regulates gene expression by activating RA receptors (RAR). By using a reporter mouse model, we recently showed that endogenous tRA/RAR signaling was present in kidney collecting duct cells, and in mouse inner medullary collecting duct cell line (mIMCD-3).
Retinoic acid receptor-dependent, cell-autonomous, endogenous retinoic acid signaling and its target genes in mouse collecting duct cells.
Specimen part
View SamplesThe Oscillation Zone (OZ) of unsynchronized roots was disected and divided into an upper (OZ2) and lower (OZ1) half .
Oscillating gene expression determines competence for periodic Arabidopsis root branching.
Age, Specimen part
View SamplesMaternal obesity is linked with increased adverse outcomes for mother and fetus. However, the metabolic impact of excessive fat accumulation within the altered hormonal context of pregnancy is not well understood. We used a murine model of obesity, the high fat diet-fed C57BL/6J mouse to determine adipose tissue-mediated molecular mechanisms driving metabolic dysfunction throughout pregnancy. Remarkably, obese mice exhibited a normalization of visceral fat accumulation at late-stage pregnancy (-53%, P<0.001 E18.5) to achieve levels comparable in mass (per gram of body weight) to that of non pregnant, control diet fed mice. Moreover, whilst obese pregnant mice showed a marked glucose intolerance and apparent insulin resistance at mid-stage pregnancy (E14.5), glucose homeostasis converged with that of lean pregnant mice at late-stage pregnancy, suggesting an unexpected amelioration of the worsening metabolic dysfunction in obese pregnant mice.
Pregnancy in obese mice protects selectively against visceral adiposity and is associated with increased adipocyte estrogen signalling.
Specimen part
View SamplesObservational studies in human suggest involvement of vitamin A/retinoic acid (RA) signaling in the regulation of airway smooth muscle (ASM) function, but the precise mechanisms by which RA impacts ASM phenotype is not clear. Here, we generated trascriptional profiles from two different models of RA-sufficient and RA-deficient mouse ASM in order to determine the molecular targets of RA in ASM (VAS/VAD, CTR/BMS)
Retinoic acid signaling is essential for airway smooth muscle homeostasis.
Specimen part
View SamplesBackground: Skeletal muscle wasting and impaired muscle function in response to mechanical ventilation and immobilization in intensive care unit (ICU) patients are clinically challenging partly due to (i) the poorly understood intricate cellular and molecular networks; and (ii) the unavailability of an animal model mimicking this condition. By employing a unique porcine model mimicking the conditions in the ICU with long-term mechanical ventilation and immobilization, we have analyzed the expression profile of skeletal muscle biopsies taken at three time points during a five-day period.
Gene expression and muscle fiber function in a porcine ICU model.
Disease, Time
View SamplesBackground: The aim of this study is to improve our understanding of the mechanisms underlying the sparing of masticatory muscles relative to limb muscles in ICU patients with acute quadriplegic myopathy (AQM) by using a unique porcine ICU model, i.e., 5-day longitudinal experiments where animals are sedated, mechanically ventilated and exposed to factors triggering AQM, such as muscle unloading, endotoxin-induced sepsis, and systemic exposure to CS and NMBA.
Mechanisms underlying the sparing of masticatory versus limb muscle function in an experimental critical illness model.
Sex, Specimen part, Disease, Disease stage, Treatment, Time
View SamplesSuccessful host defense against pathogens requires innate immune recognition of the correct pathogen associated molecular patterns (PAMPs) by pathogen recognition receptors (PRRs) to trigger the appropriate gene program tailored to the pathogen. While many PRR pathways have been shown to contribute to the innate immune response to specific pathogens, the relative importance of each pathway for the complete transcriptional program elicited has not been examined in detail. Herein, we used RNA-sequencing with wildtype and mutant macrophages to delineate the innate immune pathways responsible for the early transcriptional response to Staphylococcus aureus, a ubiquitous microorganism that can activate a wide variety of PRRs. Unexpectedly, only two PRR pathways – the Toll-like receptor (TLR) and Stimulator of Interferon Gene (STING) pathways - were identified as dominant regulators of approximately 95% of the genes that were potently induced within the first four hours of macrophage infection with live S. aureus. TLR signaling predominantly activated an inflammatory program, STING signaling activated an antiviral/type I interferon response, and both pathways contributed to a program linking innate and adaptive immunity. Only a small number of genes were induced in the absence of TLR or STING signaling, and these genes possessed a strong hypoxia signature. STING pathway activation required live S. aureus and was largely dependent on the DNA sensor cyclic guanosine-adenosine synthase (cGAS) recognition of S. aureus DNA. Interestingly, using a cutaneous infection model, we found that the TLR and STING pathways played opposite roles in host defense to S. aureus, with TLR signaling being required for protective interleukin (IL)-1? and neutrophil recruitment and STING signaling having an opposite effect. These results provide novel insights into the complex interplay of innate immune signaling pathways triggered byS. aureus and uncover opposing roles of TLR and STING in cutaneous host defense to S. aureus. Overall design: Files are labeled according to the figures in which they were used. Note, that many data files were used in multiple figures or figure panels. Files are labeled by genotype of macrophages (WT=wildtype; KO= StingGt/Gt; DKO=MyD88-/-TRIF-/-) and whether the macrophages were treated with live (Live) or heat killed (HK) or uninfected (zero hour). Labeling of time points is in the order of "minutes_replicate #." For example, "WT_HK_30_2" indicates that this is wild type mouse macrophages stimulated with heat killed bacteria at the 30-minute time point and is replicate number 2. Reads were converted into RPKM, and the RPKM for all replicates listed for a given time point were averaged to obtain the average RPKM that was used for figures and analyses. For samples listed as contributing to either figure 3 or supplemental figure 2, the replicates that do NOT end in either KO_analysis nor DKO analysis were used to determine induced genes in wild type macrophages. In contrast, the replicates that end in KO_analysis or DKO_analysis were used to determine dependence on either STING signaling or MyD88/TRIF signaling, respectively. If a replicate was used in the STING or MyD88/TRIF dependence analysis for both live and heat-killed S. aureus, "live_and_hk" was added after the dependence analysis it contributed to. Some 0h samples were used in both live and heat-killed analyses.
Opposing roles of Toll-like receptor and cytosolic DNA-STING signaling pathways for Staphylococcus aureus cutaneous host defense.
Sex, Specimen part, Cell line, Subject
View SamplesAsymmetric division of cortex/endodermal initials (CEI) in the Arabidopsis root generates two layers of ground tissue and is controlled by a finely orchestrated interplay between the transcription factors, SHORT ROOT (SHR) and SCARECROW (SCR). To understand the dynamics of the SHR/SCR regulatory network we performed microarray time course experiments using inducible versions of SHR and SCR and examined their transcriptional effects specifically in the ground tissue.
Spatiotemporal regulation of cell-cycle genes by SHORTROOT links patterning and growth.
Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
iCLIP identifies novel roles for SAFB1 in regulating RNA processing and neuronal function.
Specimen part, Disease, Cell line
View SamplesComparison of control vs SAFB1 knockdown
iCLIP identifies novel roles for SAFB1 in regulating RNA processing and neuronal function.
Disease, Cell line
View Samples