The activity of chaperone-mediated autophagy (CMA), a catabolic pathway for selective degradation of cytosolic proteins in lysosomes, decreases with age, but the consequences of this functional decline in vivo remain unknown. In this work, we have generated a conditional knockout mouse to selectively block CMA in liver. We have found that blockage of CMA causes hepatic glycogen depletion and hepatosteatosis. The liver phenotype is accompanied by reduced peripheral adiposity, increased energy expenditure, and altered glucose homeostasis. Comparative lysosomal proteomics revealed that key enzymes in carbohydrate and lipid metabolism are normally degraded by CMA and that impairment of this regulated degradation contributes to the metabolic abnormalities observed in CMA-defective animals. These findings highlight the involvement of CMA in regulating hepatic metabolism and suggest that the age-related decline in CMA may have a negative impact on the energetic balance of old organisms.
Deficient chaperone-mediated autophagy in liver leads to metabolic dysregulation.
Specimen part
View SamplesStudies of the Xenopus organizer have laid the foundation for our understanding of the conserved signaling pathways that pattern vertebrate embryos during gastrulation. Here, we use this wealth of knowledge as leverage in the design and analysis of a genomic visualization of organizer-related gene transcription. Using ectopic expression of the two major activities of the organizer, BMP and Wnt inhibition, as well as endogenous tissues, we generate a focused set of samples that represent different aspects of organizer signaling. The genomic expression values of each sample are then measured with oligonucleotide arrays. From this data, genes regulated by organizer signaling are selected and then clustered by their patterns of regulation. A new GO biological process annotation of the Xenopus genome allows us to rapidly identify clusters that are highly enriched for known gastrula patterning genes. Within these clusters, we can predict the expression patterns of unknown genes with remarkable accuracy, leading to the discovery of new organizer-related gastrula stage expression patterns for 19 genes. Moreover, the patterns of gene response observed within these clusters allow us to parse apart the contributions of BMP and Wnt inhibition in organizer function. We find that the majority of gastrula patterning genes respond transcriptionally to these activities according to only a few stereotyped patterns, allowing us to describe suites of genes that are likely to share similar regulatory mechanisms. These suites of genes demonstrate a mechanism where BMP inhibition initiates the organizer program before gastrulation, and Wnt inhibition maintains and drives the organizer program during gastrulation.
Genomic analysis of Xenopus organizer function.
Specimen part
View SamplesProfiling genes that are regulated by the expression of wheat TaRZ1 in Arabidopsis
Comparative functional analysis of wheat (Triticum aestivum) zinc finger-containing glycine-rich RNA-binding proteins in response to abiotic stresses.
Age
View SamplesThe Arabidopsis MYB96 transcription factor plays a role in abscisic acid (ABA)-mediated drought response. To obtain clues as to how MYB96 promotes drought tolerance, we carried out microarray assays using the Affymetrix GeneChip. Experiment Design: Total RNAs were isolated from whole plants of two-week-old seedling of mutant plants overexpressing MYB96, MYB96-deficient mutants, and wild-types. Three independent biological replicates were performed for each sample.
The MYB96 transcription factor regulates cuticular wax biosynthesis under drought conditions in Arabidopsis.
Age, Time
View SamplesEthnically diverse - African American, Hispanic Latino, Asian - induced pluripotent stem cell lines bioinformatics data
Derivation of Ethnically Diverse Human Induced Pluripotent Stem Cell Lines.
No sample metadata fields
View SamplesE-cadherin (E-cad) mediates cell-cell adhesion and has been proposed to suppress both invasion and metastasis. However, invasive ductal cancers retain E-cad expression in the primary tumor, circulating tumor cells, and distant metastases. We recently demonstrated that cancer cell clusters are efficient metastatic seeds. Since clusters organize through cell-cell adhesion, we tested the requirement for E-cad in genetically engineered mouse models of luminal and basal breast cancer. Loss of E-cad increased invasion and dissemination in 3D culture and in the mammary gland. However, E-cad loss also reduced cancer cell proliferation, survival, tumor cell seeding, and metastatic outgrowth in the lungs. At the transcript level, loss of E-cad was associated with increased apoptosis. Consistent with these results, inhibition of apoptosis partially rescued the metastatic phenotype of E-cad null cancer cells. We therefore propose that E-cad is an invasion suppressor, survival factor, and metastasis promoter in invasive ductal cancers. Overall design: Differential gene expression analysis between organoids isolated from adeno-Cre transduced MMTV-PyMT E-cad+/+ (r = 4 biological replicates) and adeno-Cre transduced MMTV-PyMT E-cadfl/fl (r = 5 biological replicates)
E-cadherin is required for metastasis in multiple models of breast cancer.
Specimen part, Cell line, Treatment, Subject
View SamplesMicroarray hybridization analysis was conducted to identify genes that may affect biofilm formation.
Biofilm-forming ability of Staphylococcus aureus strains isolated from human skin.
Specimen part
View SamplesA number of inhibitors of chemokine CCL2 and its receptor CCR2 are in development and may find application for treating a range of inflammatory conditions, including autoimmune and viral arthritides. Herein we sought to determine the effect of CCR2 deficiency on arthritis caused by an arthritogenic alphavirus, Chikungunya virus.
CCR2 deficiency promotes exacerbated chronic erosive neutrophil-dominated chikungunya virus arthritis.
Sex, Specimen part
View SamplesBRCA1 nestin CRE conditional knockout cortrices of P7 animals were compared to wildtype littermates to characterize the mutant phenotype.
BRCA1 tumour suppression occurs via heterochromatin-mediated silencing.
No sample metadata fields
View SamplesOocyte maturation, fertilization, and early embryonic development occur in the absence of gene transcription. Therefore, it is critical to understand at a global level the post-transcriptional events that are driving these transitions. Here, we have used a systems approach by combining polysome mRNA profiling and bioinformatics to identify RNA binding motifs in mRNAs that either enter or exit the polysome pool during mouse oocyte maturation. Association of mRNA with the polysomes correlates with active translation.
Genome-wide analysis of translation reveals a critical role for deleted in azoospermia-like (Dazl) at the oocyte-to-zygote transition.
Specimen part
View Samples