Grb14 is an endogenous inhibitor of insulin signaling
Novel Grb14-Mediated Cross Talk between Insulin and p62/Nrf2 Pathways Regulates Liver Lipogenesis and Selective Insulin Resistance.
Specimen part, Treatment
View SamplesThe objective of the study was to evalute the changes in gene expression associated to UCP2 invalidation in colon tumors from AOM/DSS-treated mice
UCP2 Deficiency Increases Colon Tumorigenesis by Promoting Lipid Synthesis and Depleting NADPH for Antioxidant Defenses.
Specimen part
View SamplesAustism spectrum disorder (ASD) is a heterogeneous behavioral disease most commonly characterized by severe impairment of social engagement and the presence of repetitive activities. The molecular etiology of ASD is still largely unknown despite a strong genetic component. Part of the difficulty in turning genetics into disease mechanisms and potentially new therapeutics is the sheer number and diversity of the genes that have been associated with ASD and ASD symptoms. The goal of this work is to use shRNA-generated models of genetic defects proposed as causative for ASD to identify the common pathways that might explain how they produce a common clinical outcome. Transcript levels of Mecp2, Mef2a, Mef2d, Fmr1, Nlgn1, Nlgn3, Pten, and Shank3 were knocked-down in mouse primary neuron cultures using shRNA/lentivirus constructs. Whole genome expression analysis was conducted for each of the knock-down cultures as well as a mock-transduced culture and a culture exposed to a lentivirus expressing luciferase. Gene set enrichment and a causal reasoning engine were employed to indentify pathway level perturbations generated by the transcript knock-down. Quantitation of the shRNA targets confirmed the successful knock-down at the transcript and protein levels of at least 75% for each of the genes. After subtracting out potential artifacts caused by transfection and viral infection, gene set enrichment and causal reasoning engine analysis showed that a significant number of gene expression changes mapped to pathways associated with neurogenesis, long-term potentiation, and synaptic activity. This work demonstrates that despite the complex genetic nature of ASD, there are common molecular mechanisms that connect many of the best established autism candidate genes. By identifying the key regulatory checkpoints in the interlinking transcriptional networks underlying autism, we are better able to discover the ideal points of intervention that provide the broadest efficacy across the diverse population of autism patients.
Transcriptomic analysis of genetically defined autism candidate genes reveals common mechanisms of action.
Specimen part, Treatment
View SamplesTo find BMAL1-regulated genes in mice pituitary gland we performed a differential microarray from wild-type vs Bmal1-/- knock-out mice
Chromatin remodeling as a mechanism for circadian prolactin transcription: rhythmic NONO and SFPQ recruitment to HLTF.
Sex, Specimen part
View SamplesContinuous contact with self-major histocompatibility complex ligands is essential for the survival of naive CD4 T cells. We have previously shown that the resulting tonic TCR signaling also influences their fate upon activation by increasing their ability to differentiate into induced regulatory T cells. To decipher the molecular mechanisms governing this process, microarray data comparing highly (Ly-6C-) and lowly (Ly-6C+) Self-reactive naive CD4 T cells were obtained.
Calcium-mediated shaping of naive CD4 T-cell phenotype and function.
Specimen part
View SamplesPurpose: Nephron progenitor cells generate nephrons, the basic units of kidney. We developed methods to culture mouse and human NPCs in their self-renewal state in vitro with full nephrogenic potentials. The RNA-seq here is used to compare the global gene expression of long-term cultured mouse NPCs and their cognate freshly isolated primary NPCs Methods: mRNA profiles were generated by deep sequencing in duplicate from E11.5, E12.5, E13.5, E16.5 and P1 primary NPCs, and from long-term cultured NPCs derived from E11.5, E13.5, E16.5 and P1 (Passage 20 and Passage 80 for each cell line). To generate rpkm values from raw data, single-end 50bp reads were mapped to the UCSC mouse transcriptome (mm9) by STAR9, allowing for up to 10 mismatches (which is the default by STAR). Only the reads aligned uniquely to one genomic location were retained for subsequent analysis. And expression levels of all genes were estimated by Cufflink10 using only the reads with exact matches. Results: The gene expression levels of the "NPC-signature genes" were firstly transformed as logarithm scales. And then the program “prcomp”, a built-in program for principal component analysis in R packages, was employed with default parameters. We evaluated the variance percentage of each principal component, and found the top 3 components accounted for 84.1% of the total variance, where PC1 accounted for 46.42%, PC2 23.87% and PC3 13.81%. Those three PCs are therefore selected as candidate principal components in the further analysis. Another program “scatterplot3d” in the R packages was used to plot the 3D view of PCA, and “ggplot2” was used in 2D view of PCA. The PCA results indicate that cultured NPCs cluster together in PCA analysis while primary NPCs segregate into early (E11.5 to E13.5) and later (E16.5, P1) NPC groups. Interestingly, cultured NPCs are close to early NPCs in both PC1 and PC2 axes, suggesting that cultured NPCs are maintained in state close to early NPCs. The close cluster of P20 and P80 NPCs show the robustness of our culture condition in maintaining stable self-renewal state of NPCs. Conclusions: Our study represents the first analysis comparing the long-term cultured NPC lines we geneated with primary NPCs, with biologic replicates, generated by RNA-seq technology. The optimized data analysis workflows reported here should provide a framework for comparative investigations of expression profiles. Our results show that NGS offers a comprehensive and more accurate quantitative and qualitative evaluation of mRNA content within a cell or tissue. We conclude that RNA-seq based transcriptome characterization would expedite genetic network analyses and permit the dissection of complex biologic functions. Overall design: mRNA profiles were generated by deep sequencing in duplicate from E11.5, E12.5, E13.5, E16.5 and P1 primary NPCs, and from long-term cultured NPCs derived from E11.5, E13.5, E16.5 and P1 (Passage 20 and Passage 80 for each cell line)
3D Culture Supports Long-Term Expansion of Mouse and Human Nephrogenic Progenitors.
Specimen part, Cell line, Subject
View SamplesThis dataset describe the transcriptomic profiling of adult brain, gonades (testis and ovaries) of adult zebrafish exposed to 20µg/L of depleted uranium for 10 days. The progeny of the exposed fishes were also analysed at two-cells stage and 96 hours post fertilization Overall design: Biological samples (adult dissected tissues and whole embryos and larvae) were tested by RNASeq in duplicates
Whole transcriptome data of zebrafish exposed to chronic dose of depleted uranium.
No sample metadata fields
View SamplesThis study supports an active role for PLZF and RAR-PLZF in leukemogenesis, identifies upregulation of CRABPI as a novel mechanism contributing to retinoid resistance and reveals the ability of the reciprocal fusion gene products to mediate distinct
RARalpha-PLZF overcomes PLZF-mediated repression of CRABPI, contributing to retinoid resistance in t(11;17) acute promyelocytic leukemia.
No sample metadata fields
View SamplesBone-marrow mesenchymal stem cells (MSCs) are plastic adherent cells that can differentiate into various tissue lineages, including osteoblasts, adipocytes and chondrocytes. However, this progenitor property is not shared by all cells within the MSC population. In addition, MSCs vary in their proliferation capacities and expression of markers. Because of heterogeneity of CD146 expression in the MSC population, we compared CD146-/Low and CD146High cells under clonal and non-clonal (sorted MSCs) conditions to determine whether this expression is associated with specific functions. CD146-/Low and CD146High MSCs did not differ in colony-forming unit-fibroblast number, osteogenic and adipogenic differentiation or in vitro hematopoietic supportive activity. However, CD146-/Low clones proliferated slightly but significantly faster than did CD146High clones. In addition, a strong expression of CD146 molecule was associated with a commitment towards a vascular smooth muscle cell lineage with upregulation of calponin-1 expression. Thus, within a bone-marrow MSC population, certain subpopulations characterized by high expression of CD146, are committed toward a vascular smooth muscle cell lineage.
CD146 expression on mesenchymal stem cells is associated with their vascular smooth muscle commitment.
Specimen part, Subject
View SamplesThe anterior pituitary-specific transcription factor POU1F1 (also called PIT-1) was initially identified and cloned as a transactivator of PRL, GH and TSH subunit genes. Different studies indicated that POU1F1 could also have other functions in these cells. The identification of new targets of this factor could be useful to obtain a better understanding of these functions.
Research resource: A genome-wide study identifies potential new target genes for POU1F1.
Specimen part
View Samples