We performed this study to compare the gene expression pattern between coronal pulp and apical pulp complex
Comparative Gene Expression Analysis of the Coronal Pulp and Apical Pulp Complex in Human Immature Teeth.
Specimen part
View SamplesManagement of severe asthma remains a challenge despite treatment with glucocorticosteroid therapy. The majority of studies investigating disease mechanisms in treatment-resistant severe asthma have previously focused on the large central airways, with very few utilizing transcriptomic approaches. The small peripheral airways, which comprise the majority of the airway surface area, remain an unexplored area in severe asthma and were targeted for global epithelial gene expression profiling in this study.
Altered Epithelial Gene Expression in Peripheral Airways of Severe Asthma.
Sex, Age, Specimen part, Disease, Subject
View SamplesChronic cold exposure causes white adipose tissue (WAT) to adopt features of brown adipose tissue, a process known as browning. Previous studies have hinted at a possible role for the transcription factor Peroxisome Proliferator-Activated Receptor alpha (PPAR) in cold-induced browning. Here we aimed to investigate the importance of PPAR in driving transcriptional changes during cold-induced browning in mice. Male wildtype and PPAR/ mice were housed at thermoneutrality (28 C) or cold (5 C) for 10 days. Whole genome expression analysis was performed on inguinal WAT. In addition, other analyses were carried out. Whole genome expression data of livers of wildtype and PPAR/ mice fasted for 24 h served as positive control for PPAR-dependent gene regulation.Cold exposure increased food intake and decreased weight of BAT and WAT to a similar extent in wildtype and PPAR/ mice. Except for plasma non-esterified fatty acids, none of the cold-induced changes in plasma metabolites were dependent on PPAR genotype. Histological analysis of inguinal WAT showed clear browning upon cold exposure but did not reveal any morphological differences between wildtype and PPAR/ mice. Transcriptomics analysis of inguinal WAT showed a marked effect of cold on overall gene expression, as revealed by principle component analysis and hierarchical clustering. However, wildtype and PPAR/ mice clustered together, even after cold exposure, indicating a similar overall gene expression profile in the two genotypes. Pathway analysis revealed that cold upregulated pathways involved in energy usage, oxidative phosphorylation, and fatty acid -oxidation to a similar extent in wildtype and PPAR/ mice. Furthermore, cold-mediated induction of genes related to thermogenesis such as Ucp1, Elovl3, Cox7a1, Cox8, and Cidea, as well as many PPAR target genes, was similar in wildtype and PPAR/ mice. Finally, pharmacological PPAR activation had a minimal effect on expression of cold-induced genes in murine WAT.Cold-induced changes in gene expression in inguinal WAT are unaltered in mice lacking PPAR, indicating that PPAR is dispensable for cold-induced browning.
The Peroxisome Proliferator-Activated Receptor α is dispensable for cold-induced adipose tissue browning in mice.
Sex
View SamplesPost-translational modifications (PTMs) of histones exert fundamental roles in regulating gene expression. During development, groups of PTMs are constrained by unknown mechanisms into combinatorial patterns, which facilitate transitions from uncommitted embryonic cells into differentiated somatic cell lineages. Repressive histone modifications such as H3K9me3 or H3K27me3 have been investigated in detail, but the role of H4K20me3 in development is currently unknown. Here we show that Xenopus laevis Suv4-20h1 and h2 histone methyltransferases (HMTases) are essential for induction and differentiation of the neuroectoderm. Morpholino-mediated knockdown of the two HMTases leads to a selective and specific downregulation of genes controlling neural induction, thereby effectively blocking differentiation of the neuroectoderm. Global transcriptome analysis supports the notion that these effects arise from the transcriptional deregulation of specific genes rather than widespread, pleiotropic effects. Interestingly, morphant embryos fail to repress the Oct4-related Xenopus gene Oct-25. We validate Oct-25 as direct target of xSu4-20h enzyme-mediated gene repression, showing by chromatin immunoprecipitaton that it is decorated with the H4K20me3 mark downstream of the promoter in normal, but not in double-morphant, embryos. Since knockdown of Oct-25 protein significantly rescues the neural differentiation defect in xSuv4-20h double-morphant embryos, we conclude that the epistatic relationship between Suv4- 20h enzymes and Oct-25 controls the transit from pluripotent to differentiation-competent neural cells. Consistent with these results in Xenopus, murine Suv4-20h1/h2 double-knockout embryonic stem (DKO ES) cells exhibit increased Oct4 protein levels before and during EB formation, and reveal a compromised and biased capacity for in vitro differentiation, when compared to normal ES cells. Together, these results suggest a regulatory mechanism, conserved between amphibian and mammals, in which H4K20me3-dependent restriction of specific POU-V genes directs cell fate decisions, when embryonic cells exit the pluripotent state.
Suv4-20h histone methyltransferases promote neuroectodermal differentiation by silencing the pluripotency-associated Oct-25 gene.
Specimen part, Treatment
View SamplesPrimary bile acids are produced in the liver whereas secondary bile acids such as lithocholic acid (LCA) are generated by gut bacteria from primary bile acids that escape the ileal absorption. Besides their well-known function as detergents in lipid digestion, bile acids are important signaling molecules mediating effects on the hosts metabolism. As energy metabolism is closely linked to aging and longevity we supplemented fruit flies (Drosophila melanogaster) with 50 mol/l LCA either for 30 days or throughout their lifetime. LCA supplementation resulted in a significant induction of the mean (+12 days), median (+10 days) and maximum lifespan (+ 11 days) in comparison to untreated control flies. This lifespan extension was accompanied by an induction of spargel (srl), the fly homolog of mammalian PPARG co-activator 1a(PGC1A. In srl mutant flies, LCA failed to induce longevity emphasizing the essential role of srl in the observed lifespan extension. In addition, the administration of antibiotics to wild type flies abrogated LCA-mediated effects on both lifespan and srl expression, suggesting a substantial contribution of the intestinal microbiota to the LCA-induced longevity.
Lithocholic Acid Improves the Survival of Drosophila Melanogaster.
Sex, Age, Specimen part
View SamplesANGPTL4 regulates plasma lipids, making it an attractive target for correcting dyslipidemia. However, ANGPTL4 inactivation in mice fed a high fat diet causes chylous ascites, an acute-phase response, and mesenteric lymphadenopathy. Here, we studied the role of ANGPTL4 in lipid uptake in macrophages and in the above-mentioned pathologies using Angptl4-hypomorphic and Angptl4-/- mice. Angptl4 expression in peritoneal and bone marrow-derived macrophages was highly induced by lipids. Recombinant ANGPTL4 decreased lipid uptake in macrophages, whereas deficiency of ANGPTL4 increased lipid uptake, upregulated lipid-induced genes, and increased respiration. ANGPTL4 deficiency did not alter LPL protein levels in macrophages. Angptl4-hypomorphic mice with partial expression of a truncated N-terminal ANGPTL4 exhibited reduced fasting plasma triglyceride, cholesterol, and non-esterified fatty acid levels, strongly resembling Angptl4-/- mice. However, during high fat feeding, Angptl4-hypomorphic mice showed markedly delayed and attenuated elevation in plasma serum amyloid A and much milder chylous ascites than Angptl4-/- mice, despite similar abundance of lipid-laden giant cells in mesenteric lymph nodes. In conclusion, ANGPTL4 deficiency increases lipid uptake and respiration in macrophages without affecting LPL protein levels. Compared with the absence of ANGPTL4, low levels of N-terminal ANGPTL4 mitigate the development of chylous ascites and an acute-phase response in mice.
Characterization of ANGPTL4 function in macrophages and adipocytes using <i>Angptl4</i>-knockout and <i>Angptl4</i>-hypomorphic mice.
No sample metadata fields
View SamplesFor up to 70 weeks we subcutaneuously injected two hundered p53R270HWAPCre mice to different insulin-like molecules (regular insulin, insulin glargine, insulin X10 (of AspB10), IGF1 or vehicle solution). Due to the mammary gland specific p53 mutation the p53R270HWAPCre mice will develop spontanously human like mammary gland tumors in about a year. We found that frequent injections to insulin like molecules decreased the mammary gland tumor latency time in this model. Next we mRNA seqeunced tumors to reveal the underlying mechanisms for the increased tumor progression. For the next generation experiment we isolated mRNA from 50 tumors (10 tumors of each stimulation group) and sequenced with the IonTorrent (40 mil reads, on average 100 bp reads) Overall design: RNA expression profiles of 50 mammary gland tumors were analyzed, 10 tumors per treatment group (chronic insulin, glargine, x10, IGF1 or vehicle exposure)
Insulin-like growth factor 1 receptor activation promotes mammary gland tumor development by increasing glycolysis and promoting biomass production.
Specimen part, Cell line, Subject
View SamplesRNA-seq was performed using the RNA extracted from the bottom half of right lobe of mouse livers. Mice fall into two groups, mutant group which express ectopic hURI and their control littermates which do not express hURI. Two time points were considered in the study, 1-week-old mice, expressing hURI since 1 week (n =3, 4 for control and mutant, respectively) and 8-week-old mice expressing hURI since 8 week (n= 4, 3 for control and mutant, respectively), as hURI is expressed since conception. Overall design: Determination of differentially expressed transcripts over two time points (1 week and 8 weeks) in mouse livers expressing hURI (1 week and 8 weeks).
Inhibition of de novo NAD(+) synthesis by oncogenic URI causes liver tumorigenesis through DNA damage.
Specimen part, Subject
View SamplesRhesus macaques (RMs) inoculated with live-attenuated Rev-Independent Nef simian immunodeficiency virus (Rev-Ind NefSIV) as adults or neonates controlled viremia to undetectable levels and showed no signs of immunodeficiency over 6-8 years of follow-up. We tested the capacity of this live-attenuated virus to protect RMs against pathogenic, heterologous SIVsmE660 challenges
Live attenuated Rev-independent Nef¯SIV enhances acquisition of heterologous SIVsmE660 in acutely vaccinated rhesus macaques.
Specimen part
View SamplesIGHV mutation status is a well-established prognostic factor in chronic lymphocytic leukemia, and also provides crucial insights into tumor cell biology and function. Currently, determination of IGHV transcript sequence, from which mutation status is calculated, requires a specialized laboratory procedure. RNA sequencing is a method that provides high resolution, high dynamic range transcriptome data that can be used for differential expression, isoform discovery, and variant determination. In this paper, we demonstrate that unselected next-generation RNA sequencing can accurately determine the IGH@ sequence, including the complete sequence of the complementarity-determining region 3 (CDR3), and mutation status of CLL cells, potentially replacing the current method which is a specialized, single-purpose Sanger-sequencing based test. Overall design: CLL cells were sequenced by mRNA-seq on the Illumina platform then subjected to the costom bioinformatic pipeline Ig-ID which yields IGH data
Immunoglobulin transcript sequence and somatic hypermutation computation from unselected RNA-seq reads in chronic lymphocytic leukemia.
No sample metadata fields
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