Oxidative stress is a hallmark of inflammation in infection or sterile tissue injury. We show that partially oxidized phospholipids of microvesicles (MVs) from plasma of patients with rheumatoid arthritis or cells exposed to oxidative stress induce activation of TLR4. MVs from healthy donors or reconstituted synthetic MVs can be converted to TLR4 agonists by limited oxidation, while prolonged oxidation abrogates the activity. Activation by MVs mimics the mechanism of TLR4 activation by LPS. However, LPS and MVs induce significantly different transcriptional response profile in mouse BMDMs with a strong inflammation-resolving component induced by the endogenous signals. MVs thus represent a ubiquitous endogenous danger signal released under the oxidative stress, which underlies the pervasive role of TLR4 signaling in inflammation.
Toll-like receptor 4 senses oxidative stress mediated by the oxidation of phospholipids in extracellular vesicles.
Sex
View SamplesTo study the physiological role of WNT4 in the postnatal ovary, a mouse strain bearing a floxed Wnt4 allele was created and mated to the Amhr2tm3(cre)Bhr strain to target deletion of Wnt4 to granulosa cells. Wnt4flox/-;Amhr2tm3(cre)Bhr/+ mice had significantly reduced ovary weights and produced smaller litters (P<0.05). Serial follicle counting demonstrated that, while Wnt4flox/-;Amhr2tm3(cre)Bhr/+ mice were born with a normal ovarian reserve and maintained normal numbers of small follicles until puberty, they had only 25.2% of the normal number of healthy antral follicles. Some Wnt4flox/-;Amhr2tm3(cre)Bhr/+ mice had no antral follicles or corpora lutea and underwent premature follicle depletion. RTPCR analyses of Wnt4flox/-;Amhr2tm3(cre)Bhr/+ granulosa cells and cultured granulosa cells that overexpress WNT4 demonstrated that WNT4 regulates the expression of Star, Cyp11a1 and Cyp19, steroidogenic genes previously identified as downstream targets of the WNT signaling effector CTNNB1. WNT4- and CTNNB1-overexpressing cultured granulosa cells were analyzed by microarray for alterations in gene expression, which showed that WNT4 also regulates a series of genes involved in late follicle development and the cellular stress response via the WNT/CTNNB1 signaling pathway. Together, these data indicate that WNT4 is required for normal antral follicle development, and may act by regulating granulosa cell functions including steroidogenesis.
WNT4 is required for normal ovarian follicle development and female fertility.
Specimen part, Treatment
View SamplesInvestigation of whole genome gene expression level changes in OASIS KO calvaria compared to wild-type calvaria.
Signalling mediated by the endoplasmic reticulum stress transducer OASIS is involved in bone formation.
Specimen part
View SamplesThe Hippocampus Consortium data set provides estimates of mRNA expression in the adult hippocampus of 99 genetically diverse strains of mice including 67 BXD recombinant inbred strains, 13 CXB recombinant inbred strains, a diverse set of common inbred strains, and two reciprocal F1 hybrids.
Genetics of the hippocampal transcriptome in mouse: a systematic survey and online neurogenomics resource.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Dynamic changes in 5-hydroxymethylation signatures underpin early and late events in drug exposed liver.
Sex, Specimen part, Treatment, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Homer1a is a core brain molecular correlate of sleep loss.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
STAT6 transcription factor is a facilitator of the nuclear receptor PPARγ-regulated gene expression in macrophages and dendritic cells.
Specimen part, Treatment, Subject, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Conserved principles of mammalian transcriptional regulation revealed by RNA half-life.
No sample metadata fields
View SamplesCopy number variation (CNV) of DNA segments has recently been identified as a major source of genetic diversity, but a more comprehensive understanding of the extent and phenotypic effect of this type of variation is only beginning to emerge. In this study we generated genome-wide expression data from 6 mouse tissues to investigate how CNVs influence gene expression.
Segmental copy number variation shapes tissue transcriptomes.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Zebrafish Pou5f1-dependent transcriptional networks in temporal control of early development.
No sample metadata fields
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