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GSE57761
Mus musculus
5 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Somatic mitochondrial DNA (mtDNA) mutations contribute to the pathogenesis of age-related disorders, including myelodysplastic syndromes (MDS). The accumulation of mitochondria harboring mtDNA mutations in patients with these disorders suggests a failure of normal mitochondrial quality-control systems. The mtDNA-mutator mice acquire somatic mtDNA mutations via a targeted defect in the proofreading function of the mtDNA polymerase, PolgA, and develop macrocytic anemia similar to that of patients with MDS. We observed an unexpected defect in clearance of dysfunctional mitochondria at specific stages during erythroid maturation in hematopoietic cells from aged mtDNA-mutator mice. Mechanistically, aberrant activation of mechanistic target of rapamycin signaling and phosphorylation of uncoordinated 51-like kinase (ULK) 1 in mtDNA-mutator mice resulted in proteasome mediated degradation of ULK1 and inhibition of autophagy in erythroid cells. To directly evaluate the consequence of inhibiting autophagy on mitochondrial function in erythroid cells harboring mtDNA mutations in vivo, we deleted Atg7 from erythroid progenitors of wildtype and mtDNA-mutator mice. Genetic disruption of autophagy did not cause anemia in wild-type mice but accelerated the decline in mitochondrial respiration and development of macrocytic anemia in mtDNA-mutator mice. These findings highlight a pathological feedback loop that explains how dysfunctional mitochondria can escape autophagy-mediated degradation and propagate in cells predisposed to somatic mtDNA mutations, leading to disease.
Publication Title
Mito-protective autophagy is impaired in erythroid cells of aged mtDNA-mutator mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Single cells from Ptenpc-/-Smad4pc-/-mTmG+ prostate tumors were isolated into single cells which were FACS-sorted for GFP+ and Tomato+ cells and RNA was purified with TRIzol (Life Technologies).
Publication Title
Targeting YAP-Dependent MDSC Infiltration Impairs Tumor Progression.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 20 Downloadable Samples
Illumina Genome Analyzer IIx, Illumina Genome Analyzer
Description
We have determined the whole genome sequence of an individual at high accuracy and performed an integrated analysis of omics profiles over a 1.5 year period that included healthy and two virally infected states. Omics profiling of transcriptomes, proteomes, cytokines, metabolomes and autoantibodyomes from blood components have revealed extensive, dynamic and broad changes in diverse molecular components and biological pathways that occurred during healthy and disease states. Many changes were associated with allele- and edit-specific expression at the RNA and protein levels, which may contribute to personalized responses. Importantly, genomic information was also used to predict medical risks, including Type II Diabetes (T2D), whose onset was observed during the course of our study using standard clinical tests and molecular profiles, and whose disease progression was monitored and subsequently partially managed. Our study demonstrates that longitudinal personal omics profiling can relate genomic information to global functional omics activity for physiological and medical interpretation of healthy and disease states. Overall design: Examination of blood component in 20 different time points over 1.5 years which includes 2 disease state and 18 healty state Related exome studies at: SRX083314 SRX083313 SRX083312 SRX083311
Publication Title
Personal omics profiling reveals dynamic molecular and medical phenotypes.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples