This dataset investigates the transcriptional effect of mitochondrial 12S rRNA hypermethylation, both by overexpressing the mitochondrial methyltransferase mtTFB1 in HeLa cells and by using A1555G cybrids, where the 12S rRNA is hypermethylated. HeLa cells overexpressing a methyltransferase-deficient mtTFB1 (mtTFB1[G65A]) and wild-type A1555A cybrids were used as controls.
Mitochondrial stress engages E2F1 apoptotic signaling to cause deafness.
Cell line
View SamplesProgressive mitochondrial respiratory chain (RC) deficiency is associated with a wide spectrum of adult-onset degenerative diseases, as well as with normal aging. We have previously generated the Deletor mice to model late-onset progressive RC defects. Here we report novel tissue-specific pathways contributing to mitochondrial disease pathogenesis, identified by gene expression analysis. We found that RC-deficient muscle fibers secrete the fasting-induced hormone, fibroblast growth factor 21 (FGF21). This response leads to fatty acid recruitment from adipocytes and resistance to high-fat-diet induced obesity in mice, but does not affect glucose or insulin metabolism. FGF21 is also induced in the muscle of mitochondrial myopathy patients and in other RC-deficient mice. These data show that skeletal muscle is an endocrine organ, which signals its energy deficiency through FGF21. Furthermore, RC deficiency in single muscle fibers initiates a global starvation response. These data have important implications for conditions with primary or secondary RC deficiency.
No associated publication
Age, Specimen part
View SamplesSeveral aspects common to a Western lifestyle, including obesity and decreased physical activity, are known risks for gastrointestinal cancers. There is an increasing amount of evidence suggesting that diet profoundly affects the composition of the intestinal microbiota. Moreover, there is now unequivocal evidence linking a dysbiotic gut to cancer development. Yet, the mechanisms through which high-fat diet (HFD)-mediated changes in the microbial community impact the severity of tumorigenesis in the gut, remain to be determined.
High-fat-diet-mediated dysbiosis promotes intestinal carcinogenesis independently of obesity.
Sex, Age, Specimen part, Treatment
View SamplesDNA microarray analysis was performed with mouse multipotent adult germline stem cells (maGSCs) and embryonic stem cells (ESCs) from different genetic backgrounds cultured under standard ESC culture conditions and under differentiation-promoting conditions by the withdrawal of Leukemia Inhibitory Factor (LIF) and treatment with Retinoic Acid (RA). The analyzed undifferentiated cell lines are very similar based on their global gene expression pattern and show 97-99% identity dependent on the analyzed background. Only 621 genes are differentially expressed in cells derived from mouse 129SV-background, and 72 genes show differences in expression in cells generated from transgenic Stra8-EGFP/Rosa26-LacZ-background. Both maGSCs and ESCs express the same genes involved in the regulation of pluripotency, and even show no differences in the expression level of these genes. When comparing maGSCs with previously published signature genes of other pluripotent cell lines we could find that maGSCs share a very similar gene expression pattern with embryonic germ cells (EGCs). Also after differentiation of maGSCs and ESCs the transcriptomes of the cell lines are nearly identical which suggests that both cell types differentiate spontaneously in a very similar way. This is the first study comparing ESCs and a pluripotent cell line derived from an adult organism (maGSCs) on transcriptome level.
Pluripotent embryonic stem cells and multipotent adult germline stem cells reveal similar transcriptomes including pluripotency-related genes.
Specimen part
View SamplesRecently, hypoxia via the transcription factor HIF-1a has been implicated to play an important role for the fate of the adaptive immune response by regulatory T cells (Treg) and T helper 17 cells (TH17) in the mouse model. However, the reports on the effect of HIF-1a are conflicting and so far no functional data in the human system are available. Therefore, we analyzed the effect of hypoxia and HIF-1a on Treg and TH17 in the human system. FACS, western blot and reporter assays clearly demonstrated that hypoxia does not up-regulate the level of HIF-1a in CD4+ T cells (THC) and microarray analysis revealed no change of the transcriptome comparing normoxia vs. hypoxia. Furthermore, we could show that HIF-1a is almost exclusively regulated via NF-kB and NFAT, whereas hydroxylation and subsequent degradation of HIF-1a had little to no effect. In addition, we showed that HIF-1a is essential for nTreg mediated suppression and for IL-17A secretion of TH17, but not for TH17 lineage commitment measured by RORt expression. In conclusion, our results demonstrated that THC have a distinct regulation of HIF-1a protein levels, which was absolutely essential for Treg and TH17 function.
No associated publication
Specimen part, Treatment, Subject
View SamplesWe compared the expression profiles of bone marrow-derived dendritic cells (BMDC) derived from Arc/Arg3.1 knockout and wildtype animals.
No associated publication
Sex, Age, Specimen part
View SamplesWe performed gene expression profiling of total RNA from brain samples derived from BSE-infected versus non-infected cynomolgus macaques (Macaca fascicularis).
Gene expression profiling of brains from bovine spongiform encephalopathy (BSE)-infected cynomolgus macaques.
Sex, Age, Specimen part
View SamplesIntroduction of mutations into intestinal stem cells leads to tumorigenesis, therefore intestinal stem cells are believed to function as cell of origin of intestinal tumors. However in the case of additional protumorigenic stimuli differentiated cells can dedifferentiate and can also give rise to intestinal tumors. Expression of stabilized -catenin (CtnnbloxEx3/+) and mutant KrasG12D/+ in all the intestinal cells by using Cre recombinase driven by the villin promoter (VilCreER) leads to rapid transformation and tumorigenesis. However, when the same mutations are introduced only into the differentited cell by the help of Xbp1sCreER mice also develop tumors.
No associated publication
No sample metadata fields
View SamplesThough it is well established that immunological functions of CD4+ T cells are time of day-dependent, the underlying molecular mechanisms remain largely obscure. To address the question whether T cells themselves harbor a functional clock driving circadian rhythms of immune function, we analyzed clock gene expression and immune responses of CD4+ T cells purified from blood of healthy subjects at different time points throughout the day. Circadian clock function as well as immune function was further analyzed in cultivated T cells and circadian clock reporter systems. We found robust rhythms of clock gene expression as well as, after stimulation, of IFN-g production and CD40L expression in both freshly isolated and in cultured CD4+ T cells. Moreover, circadian luciferase reporter activities in CD4+ T cells and in thymic sections from PER2::LUCIFERASE reporter mice suggest that endogenous T cell clock rhythms are self-sustained under constant culture conditions. Microarray analysis of stimulated CD4+ T cell cultures revealed a rhythmic regulation of the NF-kB pathway as a candidate mechanism regulating circadian immune responses. Collectively, these data demonstrate for the first time that CD4+ T cell responses are regulated by an intrinsic cellular circadian oscillator capable of driving rhythmic adaptive immune responses in vitro and in vivo.
Circadian clocks in mouse and human CD4+ T cells.
Specimen part, Time
View SamplesKv10.1 (Eag1), member of the Kv10 family of voltage-gated potassium channels, is preferentially expressed in adult brain. The aim of the present study was to unravel the functional role of Kv10.1 in the brain by generating knockout mice, where the voltage sensor and pore region of Kv10.1 was removed to render non-functional proteins through deletion of exon 7 of the KCNH1 gene using the 3 Lox P strategy. Kv10.1-deficient mice show no obvious alterations during embryogenesis and develop normally to adulthood; cortex, hippocampus and cerebellum appear anatomically normal. Other tests, including general health screen, sensorimotor functioning and gating, anxiety, social behaviour, learning and memory did not show any functional aberrations in Kv10.1 null mice. Kv10.1 null mice display mild hyperactivity and longer-lasting haloperidol-induced catalepsy, but there was no difference between genotypes in amphetamine sensitisation and withdrawal, reactivity to apomorphine and haloperidol in the prepulse inhibition tests or to antidepressants in the haloperidol-induced catalepsy. Furthermore, electrical properties of Kv10.1 in cerebellar Purkinje cells did not show any difference between genotypes. Bearing in mind that Kv10.1 is overexpressed in over 70% of all human tumours and that its inhibition leads to a reduced tumour cell proliferation, the fact that deletion of Kv10.1 does not show a marked phenotype is a prerequisite for utilising Kv10.1 blocking and/or reduction techniques, such as siRNA, to treat cancer.
Behavioural and functional characterization of Kv10.1 (Eag1) knockout mice.
Specimen part
View Samples