This SuperSeries is composed of the SubSeries listed below.
The MuvB complex sequentially recruits B-Myb and FoxM1 to promote mitotic gene expression.
Cell line
View SamplesInsulin action in adipocytes affects whole-body insulin sensitivity. Studies of adipose-specific Glut4 knockout mice have established that adipose Glut4 contributes to the control of systemic glucose homeostasis. Presumably, this reflects a role for Glut4-mediated glucose transport in the regulation of secreted adipokines. In cultured 3T3-L1 adipocytes, Rab10 GTPase is required for insulin-stimulated translocation of Glut4 (Sano et al., 2007). The physiological importance of adipose Rab10 and the significance of its role in the control of Glut4 vesicle trafficking in vivo are unknown. Here we report that adipocytes from adipose-specific Rab10 knockout mice have a ~50% reduction in glucose uptake and Glut4 translocation to the cell surface in response to insulin, demonstrating a role for Rab10 in Glut4 trafficking. Moreover, hyperinsulinemic-euglycemic clamp shows decreased whole-body glucose uptake as well as impaired suppression of hepatic glucose production in adipose Rab10 knockout mice. Thus, fully functional Glut4 vesicle trafficking in adipocytes is critical for maintaining insulin sensitivity. Comparative transcriptome analysis of perigonadal adipose tissue demonstrates significant transcriptional similarities between adipose Rab10 knockout mice and adipose Glut4 knockout mice, consistent with the notion that the phenotypic similarities between the two models are mediated by reduced insulin-stimulated glucose transport into adipocytes. Overall design: Transcriptome sequencing of perigonadal white adipose tissue
Disruption of Adipose Rab10-Dependent Insulin Signaling Causes Hepatic Insulin Resistance.
No sample metadata fields
View SamplesAlterations of chromatin modifiers are frequent in cancer but their functional consequences remain often unclear. Focusing on the Polycomb protein EZH2 that deposits H3K27me3 mark, we showed that its high expression in solid tumors is a consequence, and not a cause, of tumorigenesis. In mouse and human models, EZH2 is dispensable for prostate cancer development and restrains breast tumorigenesis. High EZH2 expression in tumors results from a tight coupling to proliferation to ensure H3K27me3 homeostasis. However, this process is malfunctioning in breast cancer. Low EZH2 expression relative to proliferation and mutations in Polycomb genes are actually of poor prognosis and occur in metastases. We show that while altered EZH2 activity consistently modulates a subset of its target genes, it promotes a wider transcriptional instability. Importantly, transcriptional changes consequent to EZH2 loss are predominantly irreversible. Our study provides an unexpected understanding of EZH2's contribution to solid tumors with important therapeutic implications.
Impaired PRC2 activity promotes transcriptional instability and favors breast tumorigenesis.
Specimen part
View SamplesPolycomb Repressive Complex 2 (PRC2) plays a key role in controlling transcriptional repression. It is thought to act at the level of the chromatin, where its enzymatic subunits Ezh1 and Ezh2 catalyse the di/tri-methylation of histone H3 on its lysine 27 (H3K27me3).
Impaired PRC2 activity promotes transcriptional instability and favors breast tumorigenesis.
Specimen part
View SamplesThe mammalian Retinoblastoma (RB) family including pRB, p107, and p130 represses E2F target genes through mechanisms that are not fully understood. In D. melanogaster, RB-dependent repression is mediated in part by the multisubunit protein complex Drosophila RBF, E2F, and Myb (dREAM) that contains homologs of the C. elegans synthetic multivulva class B (synMuvB) gene products. Using an integrated approach combining proteomics, genomics, and bioinformatic analyses, we identified a p130 complex termed DP, RB-like, E2F, and MuvB (DREAM) that contains mammalian homologs of synMuvB proteins LIN-9, LIN-37, LIN-52, LIN-54, and LIN-53/RBBP4. DREAM bound to more than 800 human promoters in G0 and was required for repression of E2F target genes. In S phase, MuvB proteins dissociated from p130 and formed a distinct submodule that bound MYB. This work reveals an evolutionarily conserved multisubunit protein complex that contains p130 and E2F4, but not pRB, and mediates the repression of cell cycle-dependent genes in quiescence.
Evolutionarily conserved multisubunit RBL2/p130 and E2F4 protein complex represses human cell cycle-dependent genes in quiescence.
No sample metadata fields
View SamplesRetinal damage causes proliferation of Muller glia, but the degree of proliferation depends on mouse strains. Muller glial proliferation was significantly promoted by the addition of GSK3 inhibitor in 129, but not in B6. We used retinal explant culture as a model for retinal damage which caused preferential photoreceptor death in a few days.
Proliferation potential of Müller glia after retinal damage varies between mouse strains.
Age, Specimen part
View SamplesStable knockdown of NET1, a RhoGEF, was achieved in AGS Gastric Cancer cells. This gene is known to be overexpressed in the disease.
A functional and transcriptomic analysis of NET1 bioactivity in gastric cancer.
Cell line
View SamplesQuiescent hair follicle (HF) bulge stem cells (SCs) differentiate to early progenitor (EP) hair germ (HG) cells, which divide to produce transit-amplifying (TA) matrix cells. EPs can revert to SCs upon injury, but whether this de-differentiation occurs in normal HF homeostasis (hair cycle), and the mechanisms regulating both differentiation and de-differentiation are unclear. Here we use lineage tracing, gain of function, transcriptional profiling, and functional assays to examine the role of observed endogenous Runx1 level changes in the hair cycle. We find that forced Runx1 expression implements hair degeneration (catagen) and simultaneously promotes changes in the quiescent bulge SC transcriptome towards a cell-state resembling the EP HG fate. This cell-state transition is functionally reversible. We propose that SC differentiation and de-differentiation are likely to occur during normal HF degeneration and niche restructuring in response to changes in endogenous Runx1 levels associated with SC location with respect to the niche.
High Runx1 levels promote a reversible, more-differentiated cell state in hair-follicle stem cells during quiescence.
Specimen part
View SamplesMemory B cells play essential roles in the maintenance of long-term immunity and may be important in the pathogenesis of autoimmune disease, but how these cells are distinguished from their nave precursors is poorly understood. To address this, it would be important to understand how gene expression differs between memory and naive B cells in order to elucidate memory-specific functions. Using model systems that help overcome the lack of murine memory-specific markers and the low frequency of antigen-specific memory and nave cells, we undertook a global comparison of gene expression between memory B cells and their naive precursors.
Systematic comparison of gene expression between murine memory and naive B cells demonstrates that memory B cells have unique signaling capabilities.
No sample metadata fields
View SamplesWhole blood RNA-seq was leveraged to explore gene expression changes induced in mice 24 hours after immunisation with a second dose of a licensed vaccine against capsular group B meningococcus, one of the vaccines components, or one of several comparator groups. Overall design: mRNA was profiled from RNA extracted from mouse whole blood, 5-6 samples per group, using an Illumina HiSeq4000
Comparative transcriptomics between species attributes reactogenicity pathways induced by the capsular group B meningococcal vaccine, 4CMenB, to the membrane-bound endotoxin of its outer membrane vesicle component.
Sex, Cell line, Subject
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