Cold triggers VEGF dependent but hypoxia independent angiogenesis in adipose tissues and anti-VEGF agents modulate adipose metabolism
Hypoxia-independent angiogenesis in adipose tissues during cold acclimation.
Sex
View SamplesWe performed miRNA and mRNA profiling in BASC cells and c-Myc depleted BASC cells. We built potential miRNA-mRNA interaction networks specific to c-Myc regulation in BASCs
c-Myc regulates self-renewal in bronchoalveolar stem cells.
Specimen part
View SamplesVariant late-infantile (vLINCL) and juvenile neuronal ceroid lipofuscinosis (JNCL) share clinical and pathological features, including lysosomal accumulation of mitochondrial ATP synthase subunit c, but the unrelated CLN6 and CLN3 genes may initiate disease via similar or distinct cellular processes. To gain insight into the NCL pathways, we established murine wild-type and vLINCL CbCln6nclf cerebellar cells and compared them to wild-type and JNCL CbCln3ex7/8 cerebellar cells. CbCln6nclf/nclf cells and CbCln3ex7/8/ex7/8 cells both displayed abnormally elongated mitochondria and reduced cellular ATP levels and, as cells aged to confluence, exhibited accumulation of subunit c protein in Lamp 1-positive organelles. However, at sub-confluence, endoplasmic reticulum PDI immunostain was decreased only in CbCln6nclf/nclf cells, while fluid-phase endocytosis and LysoTracker labeled vesicles were decreased in both CbCln6nclf/nclf and CbCln3ex7/8/ex7/8 cells, though only the latter cells exhibited abnormal vesicle subcellular distribution. Furthermore, unbiased gene expression analyses revealed only partial overlap in the cerebellar cell genes and pathways that were altered by the Cln3ex7/8 and Cln6nclf mutations. Thus, these data support the hypothesis that vLINCL and JNCL mutations trigger distinct processes that converge on a shared pathway, which is responsible for proper subunit c protein turnover and neuronal cell survival.
Distinct early molecular responses to mutations causing vLINCL and JNCL presage ATP synthase subunit C accumulation in cerebellar cells.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-wide uH2A localization analysis highlights Bmi1-dependent deposition of the mark at repressed genes.
Sex
View SamplesPolycomb group (PcG) proteins control organism development by regulating the expression of developmental genes. Transcriptional regulation by PcG proteins is achieved at least partly through the PRC2-mediated methylation on lysine 27 of histone H3 (H3K27) and PRC1-mediated ubiquitylation on lysine 119 of histone H2A (uH2A). As an integral component of PRC1, Bmi1 has been demonstrated to be critical for H2A ubiquitylation. Although recent studies have revealed the genome wide binding patterns of some of the PRC1 and PRC2 components, as well as the H3K27me3 mark, there have been no reports describing genome wide localization of uH2A. Using the recently developed ChIP-Seq technology, here we report genome wide localization of the Bmi1-dependent uH2A mark in MEF cells. Gene promoter averaging analysis indicates a peak of uH2A just inside the transcription start site (TSS) of well annotated genes. This peak is enriched at promoters containing the H3K27me3 mark and represents the least expressed genes in WT MEF cells. In addition, peak finding reveals regions of local uH2A enrichment throughout the mouse genome, including almost 700 gene promoters. Genes with promoter peaks of uH2A exhibit lower level expression when compared to genes that do not contain promoter peaks of uH2A. Moreover, we demonstrate that genes with uH2A peaks have increased expression upon Bmi1 knockout. Importantly, local enrichment of uH2A is not limited to regions containing the H3K27me3 mark. We provide evidence to suggest that DNA methylation is tightly linked to H2A ubiquitylation in high density CpG promoters. Thus, our work not only reveals Bmi1-dependent H2A ubiquitylation but also suggests that uH2A targeting in differentiated cells may employ a different mechanism from that in ES cells.
Genome-wide uH2A localization analysis highlights Bmi1-dependent deposition of the mark at repressed genes.
Sex
View SamplesThe purpose of this study was to determine which genes are differentially regulated by the E3 ligase Nrdp1 in CD8+ T cells after treatments with anti-CD3/CD28 Abs. The results demonstrate increased induction of cytotoxicity-associated genes in Nrdp1-/- mice than in Nrdp1+/+ mice after activation. Thus Nrdp1 may be involved in the regulation of TCR signaling.
K33-linked polyubiquitination of Zap70 by Nrdp1 controls CD8(+) T cell activation.
Specimen part, Treatment
View SamplesBMP4 is down-regulated in metastatic human and murine mammary tumours. Here we determined the effect of ectopic mouse Bmp4 re-expression on global gene expression patterns in orthotopic primary mammary tumours in syngeneic Balb/c mice.
BMP4 inhibits breast cancer metastasis by blocking myeloid-derived suppressor cell activity.
Sex, Specimen part
View SamplesGlobal energy balance in mammals is controlled by the actions of circulating hormones that coordinate fuel production and utilization in metabolically active tissues. Bone-derived osteocalcin, in its undercarboxylated, hormonal form, regulates fat deposition and is a potent insulin secretagogue. Here, we show that insulin receptor (IR) signaling in osteoblasts controls osteoblast development and osteocalcin expression by suppressing the Runx2 inhibitor Twist-2. Mice lacking IR in osteoblasts have low circulating undercarboxylated osteocalcin and reduced bone acquisition due to decreased bone formation and deficient numbers of osteoblasts. With age, these mice develop marked peripheral adiposity and hyperglycemia accompanied by severe glucose intolerance and insulin resistance. The metabolic abnormalities in these mice are improved by infusion of exogenous under-carboxylated osteocalcin. These results indicate the existence of a bone-pancreas endocrine loop through which insulin signaling in the osteoblast ensures osteoblast differentiation and stimulates osteocalcin production, which in turn regulates insulin sensitivity and pancreatic insulin secretion to control glucose homeostasis.
Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition.
Specimen part, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Foxl2 functions in sex determination and histogenesis throughout mouse ovary development.
Sex, Subject
View SamplesComparison of Foxl2-null ovaries to wildtype ovaries, ovaries lacking Wnt4 or Kit, or testes, throughout mouse development.
Foxl2 functions in sex determination and histogenesis throughout mouse ovary development.
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