Cellular senescence is a homeostatic program associated with tumor suppression, wound healing, and certain age related pathologies. Senescent cells display a repressive chromatin configuration thought to stably silence proliferation-promoting genes, while at the same time activate an unusual form of immune surveillance involving a secretory program referred to as the senescence-associated secretory phenotype (SASP). Here we demonstrate that senescence also involves a global remodeling of the enhancer landscape with recruitment of the chromatin reader BRD4 to newly activated super-enhancers adjacent to key SASP genes. Transcriptional profiling and functional studies indicate that BRD4 is required for the SASP and downstream paracrine signaling. Consequently, BRD4 inhibition disrupts immune cell-mediated targeting and elimination of premalignant senescent cells in vitro and in vivo. Our results identify a critical role for BRD4-bound super-enhancers in senescence immune surveillance and in the proper execution of a tumor-suppressive program. Overall design: Analysis of RNA isolated from human fibroblasts (IMR90) in proliferating, quiescent or senescent (HrasV12) conditions upon knockdown of Brd4, p65, p53, p53/RB, p16/21 or Vehicle and JQ1 treatment
BRD4 Connects Enhancer Remodeling to Senescence Immune Surveillance.
No sample metadata fields
View SamplesThe aim of this study consists in detecting genes regulated by Meis2 in the murine cochlea
Meis2 Is Required for Inner Ear Formation and Proper Morphogenesis of the Cochlea.
Specimen part
View SamplesPurpose: Asess the transcritpional changes induced upon RAB7 knock-down in melanoma (SK-Mel-28 and UACC-62) and in colon cancer (HCT-116) cell lines. Methods: mRNA profiles of tumor cell lines (SK-Mel-28, UACC-62, HCT-116) stably expressing scrambled shRNA or RAB7 shRNA (harvested at day 3 after lentiviral infection) were generated by deep sequencing, using three biological replicates per condition. The sequence reads that passed quality filters were analyzed with TopHat and Cufflinks. Validation of induced / silenced genes was performed by western blot. Results show a differential impact of RAB7 expression in the transcriptomic profile of melanoma vs non-melanoma cell lines, and support a lineage-specific role of this small GTPase in melanoma. Overall design: Examination of the mRNA profiles RAB7-depleted vs wild type cells, performed in parallel in 3 different tumor cell lines (Melanomas: SK-Mel-28 and UACC-62, Non-melanoma: HCT-116) harvested at day 3 after lentiviral infection.
RAB7 controls melanoma progression by exploiting a lineage-specific wiring of the endolysosomal pathway.
Cell line, Treatment, Subject, Time
View SamplesGene expression analysis in hLECs treated with gain of function or loss of function of MDK in human melanoma cells. Overall design: Biological triplicates of hLEC treated for 3 days with EGM-2 MV conditioned media of melanoma cells. Cell line SK-Mel-147 KD for MDK (shMDK) and its corresponding control (shCtrl (LoF) and WM164 cell line overexpressing MDK (MDK) or an empty vector (NEG) (GoF) were used to produce the conditioned media.
Whole-body imaging of lymphovascular niches identifies pre-metastatic roles of midkine.
Specimen part, Subject
View SamplesSatellite cells are the primary source of stem cells for skeletal muscle growth and regeneration. Since adult stem cell maintenance involves a fine balance between intrinsic and extrinsic mechanisms, we performed genome-wide chronological expression profiling to identify the transcriptomic changes involved during early postnatal growth till acquisition of satellite cell quiescence.
Pericytes in the myovascular niche promote post-natal myofiber growth and satellite cell quiescence.
Specimen part
View SamplesUnderstanding how developmental and environmental signals are integrated to produce specific responses is one of the main challenges of modern biology. Hormones and, most importantly, interactions between different hormones serve as crucial regulators of plant growth and development, playing central roles in the coordination of internal developmental processes with the environment. Herein, a combination of physiological, genetic, cellular, and whole-genome expression profiling approaches has been employed to investigate the mechanisms of interaction between two key plant hormones, ethylene and auxin.
Multilevel interactions between ethylene and auxin in Arabidopsis roots.
No sample metadata fields
View SamplesSatellite cells are the primary source of stem cells for skeletal muscle growth and regeneration. Since adult stem cell maintenance involves a fine balance between intrinsic and extrinsic mechanisms, we performed genome-wide chronological expression profiling to identify the transcriptomic changes involved in acquisition of muscle stem cell characteristics.
Gene Expression Profiling of Muscle Stem Cells Identifies Novel Regulators of Postnatal Myogenesis.
Age, Specimen part
View SamplesBisphenol-A is a widespread endocrine disruptor chemical. In utero or perinatal exposure to bisphenol-A (BPA), leads to impaired glucose metabolism during adulthood. To investigate the consequences of the exposure to bisphenol-A during development in pancreatic beta-cell growth
Maternal Exposure to Bisphenol-A During Pregnancy Increases Pancreatic β-Cell Growth During Early Life in Male Mice Offspring.
Sex, Specimen part
View SamplesACC Synthase (ACS) is the key regulatory enzyme in the ethylene biosynthesis in plants. It catalyzes the conversion of s-adenosylmethionine (SAM) to 1-aminocyclopropane-1-carboxylic acid (ACC), the precursor of ethylene. Arabidopsis has nine ACS genes. The goal of the project is to inactivate each gene by insertional mutagenesis and amiRNA technology and eventually construct a null ACS mutant. We have been recently able to achieve this goal. Furthermore, we wanted to know how inactivation of individual ACS genes affects global gene expression.
A combinatorial interplay among the 1-aminocyclopropane-1-carboxylate isoforms regulates ethylene biosynthesis in Arabidopsis thaliana.
No sample metadata fields
View SamplesWild-type and mouse mutants for FGF3, FGF10 and FGF3/FGF10 double mutants at embryonic day E10 were analysed by microarrays for downregulated genes. A tissue sample corresponding to an area containing the otic vesicle and surrounding mesenchyme and neighboring hindbrain were isolated from E10 embryos (See Figure 3A of manuscript). Five samples were pooled for RNA preparation. Samples were isolated from wild-type, FGF3, FGF10 and FGF3/FGF10 double mutants. Two RNA samples for each genotype were generated (corresponding to 8 tissue samples). RNA was labeled and hybridized with Affymetrix U74A V2 arrays.
FGF signalling controls expression of vomeronasal receptors during embryogenesis.
Age, Specimen part, Disease, Disease stage
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