Amyotrophic later sclerosis is a motor neuron disease accompanied by metabolic changes. PGC (PPAR gamma coactivator)-1alpha is a master regulator of mitochondrial biogenesis and function and of critical importance for all metabolically active tissues. PGC-1alpha is a genetic modifier of ALS.
ALS-causing mutations differentially affect PGC-1α expression and function in the brain vs. peripheral tissues.
Specimen partView Samples
An increasing amount of evidence suggests that the small intestine may play an important role in the development of metabolic diseases, such as obesity and insulin resistance. The small intestine provides the first barrier between diet and the body. As a result, dysregulation of biological processes and secretion of signal molecules from the small intestine may be of importance in the regulation and dysregulation of whole body metabolic homeostasis. Changes in gene expression of genes involved in lipid metabolism, cell cycle and immune response may contribute to the aetiology of diet-induced obesity and insulin resistance. In the current study we present a detailed investigation on the effects a chow diet, low fat diet and high fat diet on gene expression along the proximal-to-distal axis of the murine small intestine. The reported results provide a knowledge base for upcoming studies on the role of the small intestine in the aetiology of diet-induced diseases.
Cross-species comparison of genes related to nutrient sensing mechanisms expressed along the intestine.
Sex, Specimen partView Samples
Gene expression profiles of bipolar disorder (BD) patients were assessed during both a manic and a euthymic phase and compared both intra-individually, and with the gene expression profiles of controls.
Investigation of manic and euthymic episodes identifies state- and trait-specific gene expression and STAB1 as a new candidate gene for bipolar disorder.
Specimen part, Disease, SubjectView Samples
Asymmetric cell division results in two distinctly fated daughter cells to generate cellular diversity. A major molecular hallmark of an asymmetric division is the unequal partitioning of cell-fate determinant proteins. We have previously established that growth factor signaling promotes protein depalmitoylation to foster polarized protein localization, which in turns drives migration and metastasis. Here, we report protein palmitoylation as a key mechanism for the asymmetric partitioning of the cell-fate determinants Numb (Notch antagonist) and ß-catenin (canonical Wnt regulator) through the activity of a depalmitoylating enzyme, APT1. Using point mutants, we show specific palmitoylated residues on proteins, such as Numb, are required for asymmetric localization. Furthermore, by live-cell imaging, we show that reciprocal interactions between APT1 and CDC42 regulate the asymmetric localization of Numb and ß-catenin to the plasma membrane. This in turn restricts Notch and Wnt transcriptional activity to one daughter cell. Moreover, we show altering APT1 expression changes the transcriptional signatures to those resembling that of Notch and ß-catenin in MDA-MB-231 cells. We also show loss of APT1 depletes the population of CD44+/CD24lo/ALDH+ tumorigenic cells in colony formation assays. Together, the findings of this study demonstrate that palmitoylation, via APT1, is a major mechanism of asymmetric cell division regulating Notch and Wnt-associated protein dynamics, gene expression, and cellular functions. Overall design: Gene expression by RNAseq of MDA-MB-231 triple receptor negative breast cancer cells expressing scramble control vector, shAPT1 knockdown, and APT1wt performed in triplicate. Total of 9 samples were analyzed.
The depalmitoylase APT1 directs the asymmetric partitioning of Notch and Wnt signaling during cell division.
Specimen part, Cell line, Treatment, SubjectView Samples
IKK kinase is essential for the B cell maturation and secondary lymphoid organ development. In the current study, we evaluated the role of IKK in the marginal zone and follicular B lymphocyte development by genetically deleting IKK from the B cell lineage using CD19-Cre mice. The loss of IKK did not affect the normal development of early B cell progenitors. However, a significant decline was observed in the percentage of immature B lymphocytes, mature marginal zone and follicular B cells along with a severe disruption of splenic marginal and follicular B cell zones. A gene expression analysis performed on the RNA extracted from the newly formed B cells (B220+IgMhi) revealed that IKK deficiency produces significant changes in the expression of genes involved in MZ and FO B lymphocyte survival, homing and migration. And several among those genes identified belong to G protein family. Specifically, we validated the upregulated expression of regulator of G protein signaling 13 (RGS13), which is a GTPase activating protein (GAP) that negatively regulates G protein signaling and impede B cell migration. Likewise, promigratory B lymphocyte receptor, the sphingosine-1-phosphate receptor 3 (SIPR3) that couple to Gi showed significantly reduced expression. In addition, an in silico analysis of gene product interactions revealed NF-B signaling pathways to be a major gene regulating networks perturbed with IKK deletion. Taken together, this study reveals IKKNF-B and G protein signaling axis to be central for the MZ and FO B cells survival, maintenance, homing and migration.
IKKα deficiency disrupts the development of marginal zone and follicular B cells.
Specimen partView Samples
We prepared small RNA libraries from 29 tumor/normal pairs of human cervical tissue samples. Analysis of the resulting sequences (42 million in total) defined 64 new human microRNA (miRNA) genes. Both arms of the hairpin precursor were observed in twenty-three of the newly identified miRNA candidates. We tested several computational approaches for analysis of class differences between high throughput sequencing datasets, and describe a novel application of log linear model that has provided the most datasets, and describe a novel application of log linear model that has provided the most effective analysis for this data. This method resulted in the identification of 67 miRNAs that were differentially-expressed between the tumor and normal samples at a false discovery rate less than 0.001. Overall design: A total of 29 tumor/normal pairs of human cervical tissue samples were analyzed. Two samples (G699N_2 and G761T_2) were performed in duplicates. No Fastq files for GSM532871 to GSM532889, GSM532929, and GSM532930. Sequence files are provided as text files for these 22 Sample records in GSE20592_RAW.tar. 38 samples with quality scores are available from SRA as SRP002/SRP002326 (see Supplementary file below).
Ultra-high throughput sequencing-based small RNA discovery and discrete statistical biomarker analysis in a collection of cervical tumours and matched controls.
No sample metadata fieldsView Samples
The selective impact of pathogen epidemics on host defenses can be strong but remains transient. By contrast, life-history shifts can durably and continuously modify the balance between costs and benefits, which arbitrates the evolution of host defenses. Their impact, however, has seldom been documented. Here, we show with a simple mathematical model that the selective advantage of the defense system is expected to decrease with decreasing life span. We further document that, in natural populations of the model plant system Arabidopsis thaliana, the expression level of defense genes correlate positively with flowering time, a proxy for the length of vegetative life span. Using a genetic strategy to partition life span-dependent and â€“independent defense genes, we demonstrate that this positive co-variation is not explained by the pleiotropic action of major regulatory genes controlling both defense and life span. In agreement with our model, this study reveals that natural selection has likely assembled alleles promoting lower expression of defense genes with alleles decreasing the duration of vegetative life span in natural populations of A. thaliana. This is the first study demonstrating that life history evolution has a pervasive impact on the evolution of host immunity. Overall design: Seeds of Bur-0, Col-0 and 278 Bur-0xCol-0 Recombinant Inbred Lines (RIL) obtained after 8 generations of selfing were provided by the Arabidopsis Stock Center at INRA Versailles (France). We selected the 40 RIL in the 15% and 85% quantiles of flowering time for RNA sequencing. Each RIL and the two parental lines were planted in 20 replicates in the conditions described above. At days 14 and 28, the oldest leaf was flash-frozen in liquid nitrogen. Three pools, each combining 13 RIL, were produced at each time point for early and late lines, for a total of 3 biological replicates, 2 pool types (early and late RIL) and 2 time points (14 and 28 days). For each of the two parental lines, leaves of 12 replicates were pooled for each time point.
Assortment of Flowering Time and Immunity Alleles in Natural Arabidopsis thaliana Populations Suggests Immunity and Vegetative Lifespan Strategies Coevolve.
Specimen part, Subject, TimeView Samples
Genome-wide expression studies were performed on dermal fibroblasts from Sotos syndrome patients with a confirmed NSD1 abnormality and compared with age-sex matched controls.
Sotos syndrome is associated with deregulation of the MAPK/ERK-signaling pathway.
Specimen part, Disease, Disease stage, TreatmentView Samples
During early vertebrate development, a large number of noncoding RNAs are maternally inherited or expressed upon activation of zygotic transcription. The exact identity, expression levels, and function during early vertebrate development for most of these noncoding RNAs remains largely unknown. miRNAs (microRNAs) and piRNAs (piwi-interacting RNAs) are two classes of small non-coding RNAs that play important roles in gene regulation during early embryonic development. Here, we utilized Illumina next generation sequencing technology to determine temporal expression patterns for both miRNAs and piRNAs during four distinct stages of early vertebrate development using zebrafish as a model system. For miRNAs, the expression patterns for 192 known miRNAs and 12 novel miRNAs within 123 different miRNA families were determined. Significant sequence variation was observed at the 5'' and 3'' ends of miRNAs with a large number of extra nucleotides added in a non-template directed manner. We also identified a large and diverse set of piRNAs expressed during early development, far beyond that expected if piRNA expression is restricted to germ cells. Our analyses represent the deepest investigation to date of small RNA expression during early vertebrate development and suggest important novel functions for small RNAs during embryogenesis. Overall design: Identify the expression of small RNAs in zebrafish embryos of four different developmental stages using high through-put sequencing
Transcriptome-wide analysis of small RNA expression in early zebrafish development.
No sample metadata fieldsView Samples