This SuperSeries is composed of the SubSeries listed below.
Inherited variation in miR-290 expression suppresses breast cancer progression by targeting the metastasis susceptibility gene Arid4b.
Specimen part, Treatment
View SamplesThe mitochondrial calcium uniporter has been proposed to coordinate the organelle's energetics with cytosolic calcium signaling. Previous studies have shown that the uniporter current is extremely high in mitochondria from brown adipose tissue (BAT), yet the contribution of the uniporter to BAT physiology in vivo is not known. Here, we report the generation and characterization of a mouse model lacking Mcu, the pore forming subunit of the uniporter, specifically in BAT (BAT-Mcu-KO). BAT-Mcu-KO mice are born in Mendelian ratios on a C57BL6/J genetic background, without any overt phenotypes. Although uniporter based calcium uptake is selectively ablated in BAT mitochondria, these mice are able to defend their body temperature in response to cold challenge and exhibit a normal body weight trajectory on a high fat diet. BAT transcriptional profiles at baseline and following cold-challenge are intact and not impacted by loss of Mcu. Unexpectedly, we found that cold powerfully activates the ATF4-dependent integrated stress response in BAT, and increases both circulating FGF21 and GDF15 levels, raising the hypothesis that the integrated stress response partly underlies the pleiotropic effects of BAT on systemic metabolism. Our study demonstrates that the uniporter is largely dispensable for BAT thermogenesis, and unexpectedly, uncovers a striking activation of the integrated stress response of BAT to cold challenge. Overall design: RNA-seq was performed on BAT RNA isolated from BAT-Mcu-KO and control animals housed for 6 hours at 4C or room temp (RT). Samples include 6 control animals at RT; 5 control animals at 4C; 6 BAT-Mcu-KO animals at RT; and 6 BAT-Mcu-KO animals at 4C.
Exploring the In Vivo Role of the Mitochondrial Calcium Uniporter in Brown Fat Bioenergetics.
Sex, Specimen part, Cell line, Subject
View SamplesmiRNA sequencing of mammary tumor RNA from 18 [AKXD subline(n) x PyMT]F1. The PyMT strain was FVB/N-TgN(MMTV-PyVT)634Mul. Overall design: Mammary tumor total small RNA from mice representing each of the 18 AKXD RI strains was pooled to represent each strain and sequenced using the Illumina Genome Analyzer IIx sequencer.
An integrated systems genetics screen reveals the transcriptional structure of inherited predisposition to metastatic disease.
Specimen part, Cell line, Subject
View SamplesmRNA expression data from mammary tumors extracted 30 days after orthotopic injection of miR-290-expressing and negative control 6dt1 cells into female FVB/N mice.
Inherited variation in miR-290 expression suppresses breast cancer progression by targeting the metastasis susceptibility gene Arid4b.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genetic background may contribute to PAM50 gene expression breast cancer subtype assignments.
Specimen part
View SamplesMouse genetic crosses were established between the PyMT model of metastatic breast cancer and MOLF/Ei strain. Tumors were harvested from the animals for gene expression analysis to identify genes associated with progression to distant metastatic disease.
Genetic background may contribute to PAM50 gene expression breast cancer subtype assignments.
Specimen part
View SamplesMouse genetic crosses were established between the PyMT model of metastatic breast cancer and the G5 generation of the Diversity Outcross (DO). Tumors were harvested from the animals for gene expression analysis to identify genes associated with progression to distant metastatic disease.
Genetic background may contribute to PAM50 gene expression breast cancer subtype assignments.
Specimen part
View SamplesMicroarray time-course of mouse myotubes transduced with the transcriptional co-activator PGC-1alpha, which is known to induce mitochondrial biogenesis in muscle cells.
Systematic identification of human mitochondrial disease genes through integrative genomics.
Cell line
View SamplesMitochondrial defects are associated with a spectrum of human disorders, ranging from rare, inborn errors of metabolism to common, age-associated diseases such as diabetes and neurodegeneration. In lower organisms, genetic retrograde signaling programs have been identified that promote cellular and organism survival in the face of mitochondrial dysfunction. Here, we characterized the transcriptional component of the human mitochondrial retrograde response in an inducible model of mitochondrial dysfunction.
Mitochondrial dysfunction remodels one-carbon metabolism in human cells.
Cell line
View SamplesWe microdissected each compartment from 6-micron paraffin sections using the Leica AS LMD system to identify all genes active in different compartments of a soybean seed containing globular-stage embryos.
Using genomics to study legume seed development.
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