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SRP050090
Mus musculus
4 Downloadable Samples
Illumina HiSeq 2000
Description
Obesity is linked to the development of metabolic disorders. Expansion of white adipose tissue (WAT) from hypertrophy of pre-existing adipocytes and/or differentiation of precursors into new mature adipocytes contributes to obesity. We found that Nck2 expression is largely restricted to WAT, raising the hypothesis that it may play a unique function in that tissue. Using mice lacking Nck2, we found that Nck2 regulates adipocyte hypertrophy thus contributing to increased adiposity and progressive glucose intolerance, insulin resistance and hepatic steatosis. These findings were recapitulated in humans such that Nck2 expression in omental WAT was inversely correlated with the degree of obesity. Mechanistically, Nck2 deficiency promoted the induction of an adipocyte differentiation program and signaling by the PERK-eIF2a-ATF4 pathway in agreement with a role for the unfolded protein response in adipogenesis. These findings uncover Nck2 as a novel regulator of adipogenesis and that perturbation in its functionality contributes to adiposity-related metabolic disorders. Overall design: Differential gene expression profile between epididymal white adipose tissue of Nck2-/- and Nck2+/+ mice by RNA sequencing (Illumina HiSEq 2000)
Publication Title
Nck2 Deficiency in Mice Results in Increased Adiposity Associated With Adipocyte Hypertrophy and Enhanced Adipogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 28 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The white adipose tissue (WAT) rapidly loses mass when mice are fed a diet containing trans-10, cis-12 conjugated linoleic acid (t10c12 CLA). A microarray analysis of WAT due to CLA feeding was performed to better define the processes and genes involved. WAT weight decreased by ca. 80% over 17 days of feeding a 0.5% t10c12 CLA diet. The lipid volume decreased by 90% and the number of adipocytes and total cells were reduced by15% and 47%, respectively. Microarray profiling of replicated pools of control and treated mice (n=140) at seven time points over the 17day feeding indicated between 2798 to 4318 genes showed mRNA changes of 2-fold or more. Transcript levels for genes of glucose and fatty acid import or biosynthesis were significantly reduced. A prolific inflammation response was indicated by the 2 to100-fold induction of many cytokine transcripts, including those for IL-6, IL1?, TNF ligands, and CXC family members
Publication Title
Trans-10, cis-12 conjugated linoleic acid causes inflammation and delipidation of white adipose tissue in mice: a microarray and histological analysis.
Sample Metadata Fields
Age
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Identification of filamin-A as a target for insulin and IGF1 action.
Publication Title
Genome-Wide Analyses Identify Filamin-A As a Novel Downstream Target for Insulin and IGF1 Action.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 24 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Trans-10, Cis-12 conjugated linoleic acid (t10c12 CLA) causes fat loss in mouse 3T3-L1 adipocyte tissue culture. The early transcriptome changes were analyzed using high-density microarrays to better characterize the signaling pathways responding to t10c12 CLA. Their gene expression responses between 4 to 24 hr after treatment showed a common set of early gene expression changes indicative of an integrated stress response (ISR).
Publication Title
Trans-10, cis-12 conjugated linoleic acid activates the integrated stress response pathway in adipocytes.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Trans-10, Cis-12 conjugated linoleic acid (t10c12 CLA) causes fat loss in mouse white adipose tissue (WAT). The early transcriptome changes in WAT were analyzed using high-density microarrays to better characterize the signaling pathways responding to t10c12 CLA. Their gene expression responses between 4 to 24 hr after treatment showed a common set of early gene expression changes indicative of an integrated stress response (ISR).
Publication Title
Trans-10, cis-12 conjugated linoleic acid activates the integrated stress response pathway in adipocytes.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Trans-10, Cis-12 conjugated linoleic acid (t10c12 CLA) causes fat loss in mouse white adipose tissue (WAT) and 3T3-L1 adipocyte tissue culture; however in preadipocyte tissue (this series) the UPS/ISR and fat loss is not detected. The early transcriptome changes in 3T3-L1 preadipocyte tissue culture were analyzed using high-density microarrays to better characterize the signaling pathways responding to t10c12 CLA. Their gene expression responses between 4 to 12 hr after treatment do not show a set of genes indicative of an integrated stress response (ISR).
Publication Title
Trans-10, cis-12 conjugated linoleic acid activates the integrated stress response pathway in adipocytes.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Trans-10, Cis-12 conjugated linoleic acid (t10c12 CLA) causes fat loss in mouse 3T3-L1 adipocyte tissue culture; however cis-9, trans-11 CLA does not (this series). The early transcriptome changes were analyzed using high-density microarrays to better characterize the signaling pathways responding to c9t11 CLA. Their gene expression responses between 8 to 12 hr after treatment showed no gene expression changes indicative of an integrated stress response (ISR).
Publication Title
Trans-10, cis-12 conjugated linoleic acid activates the integrated stress response pathway in adipocytes.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Tunycamcin induces UPR/ISR and Inflammation in mouse 3T3-L1 adipocyte tissue culture. The early transcriptome changes were analyzed using high-density microarrays to better characterize the signaling pathways responding to tunicamycin, to be compared with similar experiments with CLA as the treatment. Their gene expression responses between 4 to 12 hr after treatment showed a common set of early gene expression changes indicative of a UPR/Inflammation stress response.
Publication Title
Trans-10, cis-12 conjugated linoleic acid activates the integrated stress response pathway in adipocytes.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Human induced pluripotent stem cells (hiPSCs) provide an invaluable source for regenerative medicine; but are limited by proficient lineage specific differentiation. Here we reveal that hiPSCs derived from dermal skin fibroblasts (Fib) vs. human cord blood (CB) cells exhibit equivalent and indistinguishable pluripotent properties, but harbor important propensities for neural and hematopoietic lineage differentiation, independent of reprogramming factors used. Genes associated with germ layer specification were identical in both Fib or CB derived iPSCs; whereas patterns of lineage specific marks emerge upon differentiation induction of hiPSCs that were correlated to the cell type of origin used to create hiPSCs. Functionally, CB-iPSCs predominantly differentiate into hematopoietic cells and even adopt definitive hematopoiesis as evidenced by adult -globin positive red blood cell development whereas Fib-iPSCs possess enhanced neural capacity. These clear differentiation propensities come at the expense of other lineages and cannot be overcome with additional external stimuli for alternative cell fates. Moreover, these differences in developmental potential are encoded within cultures of CB vs. Fib derived hiPSCs that can be used to predict differentiation propensity.
Publication Title
Somatic transcriptome priming gates lineage-specific differentiation potential of human-induced pluripotent stem cell states.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 83 Downloadable Samples
- Illumina HiSeq 1500
Description
Human pluripotent stem cells (hPSCs) have been reported in naïve and primed states. However, the ability of human PSCs to generate mature cell types is the only imperative property for translational utility. Here, we reveal that the naïve state enhances self-renewal capacity while restricting lineage differentiation in vitro to neural default fate. Gene expression analyses indicate expression of multiple lineage associated transcripts in naïve hPSCs and thus failed to predict biased functional differentiation. Naïve hPSCs can be converted to primed allowing recovery of multilineage differentiation over long serial passage or immediately through suppression of OCT4 but not NANOG. To this end, we identified chemical inhibitors of OCT4 expression that acutely restore naïve hPSC differentiation. Our study identifies unique cell fate features and critical restrictions in human pluripotent states, and provides an approach to overcome these barriers that harness both efficient naïve hPSC growth whilst maintaining in vitro differentiation capacities essential for hPSC applications. Overall design: hPSC lines were transduced with shRNA lentiviruses in order to assess the effects of reducing NANOG and OCT4 gene expression on differention in the naïve state. shRNA expressing cells were sorted and then total RNA was extracted in order to perform transcriptome profiling by RNA-seq. Each experimental condition involves 2 technical replicates of 2 biological replicates (2 tech X 2 biol = 4 reads).
Publication Title
Lineage-Specific Differentiation Is Influenced by State of Human Pluripotency.
Sample Metadata Fields
Specimen part, Subject
View Samples