The premature aging disorder Werner Syndrome (WS) is characterized by early onset of aging phenotypes resembling natural aging. In most WS patients there are mutations in the DNA helicase WRN, an enzyme important in maintaining genome stability and telomere replication. Interestingly, its clinical manifestations reflect a severe degree of deterioration for connective tissue, whereas the central nervous system is less affected. We suggest that the varied vulnerability to aging is regulated by an unknown mechanism that protects specific lineages of stem cells from premature senescence. To address this problem, we reprogrammed patient skin fibroblasts to induced pluripotent stem cells (iPSC). The expression profile for the differentiated normal and WS fibroblasts and undifferentiated iPSC were compared. A distinct expression profile was found between normal and WS fibroblasts, however, few changes of gene expression were found in iPSC. Our findings suggest an erasure of aging phenotype associated with WS in reprogrammed iPSC.
Telomerase protects werner syndrome lineage-specific stem cells from premature aging.
Sex, Age, Specimen part
View SamplesAberrant methylation has been postulated to play an important role in tumorigenesis. We report the use of methylated DNA immunoprecipitation (MeDIP) and whole-genome tiling arrays to investigate methylation changes in testicular germ cell tumor (TGCT) cells. Coupled to expression profiling changes, we found that only 22-26% of differentially methylated genes were also expressed differentially. This phenomenon was independent of the presence of CpG islands in the promoter. Differential methylation and expression of some of these genes were confirmed in testicular tumor tissue. A substantial number of differentially methylated regions in the human genome were not linked to annotated gene loci. Subsequent analysis indicated several microRNAs and small nucleolar RNAs were regulated by these differentially methylated regions. Our results demonstrate the power of the combination of MeDIP-chip analysis and expression profiling for discovery in cancer cells of epigenetically regulated genes and non-coding RNAs in cancer cells.
Genome-wide DNA methylation profiling reveals novel epigenetically regulated genes and non-coding RNAs in human testicular cancer.
Sex, Age, Specimen part, Cell line
View SamplesSmall RNAs (sRNA) that act by base pairing with trans-encoded mRNAs modulate metabolism in response to a variety of environmental stimuli. Here, we describe an Hfq-binding sRNA (FnrS) whose expression is induced upon a shift from aerobic to anaerobic conditions and which acts to down regulate the levels of a variety of mRNAs encoding metabolic enzymes. Anaerobic induction in minimal medium depends strongly on FNR but is also affected by ArcA and CRP. Whole genome expression analysis showed that the levels of at least 32 mRNAs are down regulated upon FnrS overexpression, 15 of which are predicted to base pair with FnrS by TargetRNA. The sRNA is highly conserved across its entire length in numerous enterobacteria, and mutation analysis revealed that two separate regions of FnrS base pair with different sets of target mRNAs. The majority of the target genes previously reported to be down regulated in an FNR-dependent manner lack recognizable FNR binding sites. We thus suggest that FnrS extends the FNR regulon and increases the efficiency of anaerobic metabolism by repressing the synthesis of enzymes that are not needed under these conditions.
Reprogramming of anaerobic metabolism by the FnrS small RNA.
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View SamplesBacteria selectively consume some carbon sources over others through a regulatory mechanism termed catabolite repression. Here, we show that the base pairing RNA Spot 42 plays a broad role in catabolite repression in Escherichia coli by directly repressing genes involved in central and secondary metabolism, redox balancing, and the consumption of diverse non-preferred carbon sources. Many of the genes repressed by Spot 42 are transcriptionally activated by the global regulator CRP. Since CRP represses Spot 42, these regulators participate in a specific regulatory circuit called a multi-output feedforward loop. We found that this loop can reduce leaky expression of target genes in the presence of glucose and can maintain repression of target genes under changing nutrient conditions. Our results suggest that base pairing RNAs in feedforward loops can help shape the steady-state levels and dynamics of gene expression.
The base-pairing RNA spot 42 participates in a multioutput feedforward loop to help enact catabolite repression in Escherichia coli.
Specimen part
View SamplesWe screened for differentially expressed genes in the developing notochord using the Affymetrix microarray system in Xenopus laevis. At late gastrula, we dissected four regions from the embryo, anterior mesoderm, posterior mesoderm, notochord and presomitic mesoderm. Three types of comparison were carried out to generate a list of predominantly notochord expressed genes: (1) Posterior mesoderm vs. anterior mesoderm; notochord genes are expected to be increased since the notochord is located in the posterior mesoderm. (2) Posterior mesoderm vs. whole embryos; notochord genes are expected to be increased. (3) Notochord vs. somite. This comparison sub-divided the group of posterior mesodermal genes identified in (1) and (2). All tissues are dissected using tungsten needles. We first dissected dorsal tissue above the archenteron from late gastrula to early neurula. To loosen tissue, we treated the dissected dorsal explant in a 1% cysteine solution (pH 7.4) and removed the neuroectodermal layer. Anterior mesoderm was dissected corresponding to about the anterior one-third of the archenteron roof, and the rest was collected as posterior mesoderm. The posterior mesodermal explant was dissected into notochord and somites, following a clearly visible border between the two tissues. The accuracy of all dissection was confirmed by RT-PCR of marker genes.
Coordinated activation of the secretory pathway during notochord formation in the Xenopus embryo.
Specimen part
View SamplesWe used microarrays to detail the global programme of gene expression underlying the disease progression in the mutant mice compared to their control littermates.
Microarray expression analysis and identification of serum biomarkers for Niemann-Pick disease, type C1.
Sex, Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Night/day changes in pineal expression of >600 genes: central role of adrenergic/cAMP signaling.
Specimen part, Time
View SamplesTemporal changes of gene expression from 1-wk- to 4-wk and 8-wk-old mouse in heart, kidney and lung. Mammalian somatic growth is rapid in early postnatal life but then slows and eventually ceases in multiple tissues. We hypothesized that there exists a postnatal gene expression program that is common to multiple tissues and is responsible for this coordinate growth deceleration. Consistent with this hypothesis, microarray analysis identified >1600 genes that were regulated with age coordinately in kidney, lung, and heart of juvenile mice, including many genes that regulate proliferation. As examples, we focused on three growth-promoting genes, Igf2, Mest, and Peg3, that were markedly downregulated with age. We conclude that there exists an extensive genetic program occurring during postnatal life. Many of the involved genes are regulated coordinately in multiple organs, including many genes that regulate cell proliferation. At least some of these are themselves apparently regulated by growth, suggesting that, in the embryo, a gene expression pattern is established that allows for rapid somatic growth of multiple tissues but then, during postnatal life, this growth leads to negative-feedback changes in gene expression that in turn slow and eventually halt somatic growth, thus imposing a fundamental limit on adult body size.
An extensive genetic program occurring during postnatal growth in multiple tissues.
Sex, Age, Specimen part
View SamplesTurner Syndrome (TS) is the most common X chromosome aneuploidy disorder in female, and the predominant karyotype is 45X, a complete loss of the second sex chromosome. Depending on the parental origin of the single X chromosome, 45X patients can be further divided into two groups: 45Xm and 45Xp with maternal and paternal inherited X chromosome, respectively. TS patients of 45Xm and 45Xp are found to associate with different severity in phenotype, including prevalence for cardiovascular disease.
No associated publication
Sex
View SamplesBiological processes are optimized by circadian and circannual biological timing systems. In vertebrates, the pineal gland plays an essential role in these systems by converting time into a hormonal signal, melatonin; in all vertebrates, circulating melatonin is elevated at night, independent of lifestyle. At night, sympathetic input to the pineal gland, originating from the circadian clock in the suprachiasmatic nucleus, releases norepinephrine. This adrenergic stimulation causes an elevation of cAMP, which is thought to regulate many of the dramatic changes in genes expression known to occur at night. In many aspects, the adrenergic/cAMP effects on gene expression can be recapitulated in primary organ culture.
Night/day changes in pineal expression of >600 genes: central role of adrenergic/cAMP signaling.
Specimen part, Time
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