Thymic epithelial cells (TECs) are essential for thymopoiesis and form a complex three-dimensional network, the organization of which is strikingly different from other epithelia. Interestingly, TECs express simple epithelia keratins in the cortex, stratified epithelia keratins in the medulla and epidermal differentiation markers in Hassall's bodies. Here we investigate the relationship between thymic epithelium and epidermal differentiation and show that the thymus of the rat contains a population of clonogenic TECs that can be extensively cultured and cloned using conditions developed for epidermal cell therapy in human. Clonogenic TECs conserve a thymic identity and the capacity to integrate in a thymic epithelial network, but they acquire new functionalities when exposed to an inductive skin microenvironment, permanently adopting the fate of hair follicle multipotent stem cells. This change in fate, maintained over time in serial transplantation, correlates with a down-regulation of transcription factors important for thymic identity, and an up-regulation of epidermal markers. Consequently, the TECs capacity to integrate in a thymic epithelial network is altered or even lost. Our results demonstrate that the thymus contains a population of holoclone-like epithelial cells that can function as bona fide multipotent keratinocyte stem cells, and that microenvironmental cues are sufficient to re-direct epithelial-cell fate, allowing crossing of primitive germ layer boundaries from endoderm to ectoderm.
Microenvironmental reprogramming of thymic epithelial cells to skin multipotent stem cells.
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View SamplesThere are concerns regarding possible reproductive toxicity from consumption of soy including an increased risk of endometriosis and endometrial cancer. We used global uterine gene expression profiles in adult ovariectomized (OVX) female rats assessed by RNAseq to examine the estrogenicity of soy protein isolate (SPI) and the potential for feeding SPI to alter estrogen signaling in the uterus. Rats were fed AIN93G diets made with casein (CAS) or SPI from postnatal day (PND) 30. Rats were OVX on PND 50 and infused with 17 beta-estradiol (E2) or vehicle. E2 increased uterine wet weight (P<0.05) and significantly altered expression of 2084 uterine genes. In contrast, SPI feeding had no effect on uterine weight and only altered expression of 177 genes. Overlap between E2 and SPI genes was limited to 69 genes (3%). GO analysis indicated significant differences in uterine biological processes affected by E2 and SPI and little evidence for recruitment of ER alpha to the promoters of ER-responsive genes after SPI feeding. The major E2 up-regulated uterine pathways were cancer pathways and extracellular organization. SPI feeding up-regulated uterine PPAR signaling and fatty acid metabolism. The combination of E2 and SPI feeding resulted in significant regulation of 715 fewer genes relative to E2 alone. In a separate experiment, the combination of E2 and SPI reversed the ability of E2 to induce uterine proliferation in response to the carcinogen dimethybenz(a)anthracene (DMBA). These data suggest SPI does not act as a weak estrogen in the uterus but appears to be a selective estrogen receptor modulator (SERM) interacting with a small sub-set of E2-regulated genes and to be anti-estrogenic in the presence of endogenous estrogens. Overall design: Rat uterus mRNA of ovariectomized adult female rats subject to four different diets (Caseine, Caseine + E2, Soy and Soy+E2 ) were sequenced, in triplicate, in an Illumina GAIIx sequencer.
RNA-sequencing data analysis of uterus in ovariectomized rats fed with soy protein isolate, 17β-estradiol and casein.
No sample metadata fields
View SamplesAppropriate nutrition during early development is essential for optimal bone mass accretion; however, linkage between early nutrition, childhood bone mass and prevention of bone loss later in life has not been extensively studied. In this report, we have demonstrated several fundamental issues in the field. 1) A significant prevention of ovariectomy (OVX) -induced bone loss from adult rats can occur with only 14 days consumption of a blueberry-containing diet immediately prior to puberty. 2) The molecular mechanisms underlying these effects involve increased myosin production and preserved a shuttle for transcription factors such as Runx2 from cytoplasm to nucleolus which stimulates osteoblast differentiation and reduces mesenchymal stromal cell senescence. 3) The effects of blueberry diet on preserving fidelity of osteoblast differentiation also overcome reduced osteoblast differentiation and activity due to OVX-induced degradation of collagen matrix.
Feeding blueberry diets in early life prevent senescence of osteoblasts and bone loss in ovariectomized adult female rats.
Sex, Specimen part
View SamplesSoy foods have been suggested to have both positive health benefits and potentially adverse effects largely as a result of their content of isoflavone phytoestrogens. Since soy protein isolate (SPI) contains isoflavones, in addition to purported health benefits, safety concerns have been raised regarding the use of SPI and soy formulas, because of potential estrogenic actions during the neonatal period, including the potential for reproductive toxicity, infertility, and the possibility of increased risk for development and recurrence of estrogen sensitive cancers such as breast cancer. In the current study, we used a rat model to compare the effects of SPI with those of 17b-estradiol (E2), on global gene expression profiles and morphology in the female rat mammary gland. Rats were either fed AIN-93G diets containing casein (CAS) or SPI beginning on postnatal day (PND) 30.
Mammary gland morphology and gene expression differ in female rats treated with 17β-estradiol or fed soy protein isolate.
Sex
View SamplesIllumina microarray experiment on BEAS-2B cells. Cells were seeded 24 h before TNF-a/IL-4 (50 ng/ml) treatment that lasted for 18 h. Cytoplasmic RNA of both normal and activated BEAS-2B cells were collected for microarray. Cells were seeded 24 h before TNF-a/IL-4 (50 ng/ml) treatment that lasted for 18 h.
Coordinated changes in mRNA turnover, translation, and RNA processing bodies in bronchial epithelial cells following inflammatory stimulation.
No sample metadata fields
View SamplesThe majority of babies in the US are formula-fed instead of breast fed. There are major differences in the composition of formulas and breast milk and yet little is known about metabolic differences in babies as the result of feeding these very different diets and how that might affect development or disease risk in later life. One concern is that soy-based formulas might have adverse health effects in babies as a result of the presence of low levels of estrogenic phytochemicals genistein and daidzein which are normally present in soy beans. In the current study, we used a piglet model to look at this question. Piglets were either fed breast milk from the sow or were fed two different infant formulas (cows milk-based or soy-based) from age 2 days to 21 days when pigs are normally weaned onto solid food. Blood glucose and lipids were measured. Formula-fed pigs were found to have lower cholesterol than breast fed piglets and in addition had larger stores of iron in their liver.Microarray analysis was carried out to see if changes in liver gene expression could explain these effects of formula feeding. It was found that overall gene expression profiles were influenced by formula feeding compared to breast fed neonates. Gender-independent and unique effects of formula influenced cholesterol and iron metabolism. Further, soy formula feeding in comparison to milk-based formula failed to reveal any estrogenic actions on hepatic gene expression in either male or female pigs.
Formula feeding alters hepatic gene expression signature, iron and cholesterol homeostasis in the neonatal pig.
Sex
View SamplesThe aim of the present study is to combine LCM and microarray analysis to study how astrocytes in the spinal cord of transgenic SOD1 G93A mice and their non-transgenic (NTg) littermates respond to stimuli determined by the presence of the human mutant protein throughout the evolution of the disease by looking at the symptomatic and late-stage disease time points.
Lysosomal and phagocytic activity is increased in astrocytes during disease progression in the SOD1 (G93A) mouse model of amyotrophic lateral sclerosis.
Sex, Age, Specimen part
View SamplesThe objective of this study was to examine relationships between weight loss through changes in lifestyle and peripheral blood gene expression profiles. Substantial weight loss (-15.2+3.8%) in lifestyle participants was associated with improvement in selected cardiovascular risk factors and significant changes in peripheral blood gene expression from pre- to post-intervention: 132 unique genes showed significant expression changes related to immune function and inflammatory responses involving endothelial activation.
Importance of substantial weight loss for altering gene expression during cardiovascular lifestyle modification.
Sex, Age, Specimen part
View SamplesRNA-seq was used to assess mRNA transcript abundance in wild type and fra2? S. cerevisiae (BY4741) cells treated with 2-(6-benzyl-2-pyridyl)quinazoline (BPQ) and CuSO4. BPQ potentiates copper toxicity and in yeast, in common with other organisms, a major cause of copper toxicity is damage of iron-sulphur clusters. Iron sensing within yeast relies on mitochondrial iron-sulphur cluster biosynthesis and therefore treatment with BPQ and copper can be used to mimic iron deficiency. Fra2 is known to be a key component of the iron sensing mechanism; however, this mechanism can operate, to an extent, independently of Fra2. BPQ (+CuSO4) treatment was used with the aim of probing the regulation of the iron regulon of S. cerevisiae and the role of Fra2 in the suppression of the low iron response. This study has uncovered nine new Cth2 target-transcripts, plus a new Aft1 target-gene and paralogous non-target. Fra2 dominates basal repression of the iron regulon in iron-replete cultures, however, Fra2-independent control of the iron regulon is also observed with CTH2 appearing to be atypically Fra2-dependent. Transcripts from untreated and CuSO4 treated cells were included as controls. Overall design: Three independent biological replicates were analysed for each condition (BPQ and CuSO4 treated wild type and fra2? cells, CuSO4 treated wild type and fra2? cells and untreated wild type and fra2? cells)
A chemical potentiator of copper-accumulation used to investigate the iron-regulons of Saccharomyces cerevisiae.
Cell line, Treatment, Subject
View SamplesFluorescent-labeled zebrafish RAS-induced embryonal rhabdomyosarcoma (ERMS) were created to facilitate in vivo imaging of tumor-propagating cells, regional tumor heterogeneity, and dynamic cell movements in diverse cellular compartments. Using this strategy, we have identified a molecularly distinct ERMS cell subpopulation that expresses high levels of myf5 and is enriched for ERMS-propagating potential when compared with other tumor-derived cells.
In vivo imaging of tumor-propagating cells, regional tumor heterogeneity, and dynamic cell movements in embryonal rhabdomyosarcoma.
Specimen part, Disease, Disease stage
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