Rheumatoid arthritis is an autoimmune disease in which joint inflammation lead to progressive cartilage and bone destruction. Matrix metalloproteinases (MMP) implicated in homeostasis of extracellular matrix (ECM) play a central role in cartilage degradation. The aim of this study was to investigate the role of MMP-8 (collagenase-2) suppression in the K/BxN serum-transfer arthritis model.
Matrix metalloproteinase-8 deficiency increases joint inflammation and bone erosion in the K/BxN serum-transfer arthritis model.
Specimen part
View SamplesBladder cancer (BC) is a highly prevalent human disease in which Rb pathway inactivation and epigenetic alterations are common events. However, the connection between these two processes is still poorly understood. Here we show that the in vivo inactivation of all Rb family genes in the mouse urothelium is sufficient to initiate BC development. The characterization of the mouse tumors revealed multiple molecular features of human BC, including the activation of E2F transcription factor and subsequent Ezh2 expression, and the activation of several signaling pathways previously identified as highly relevant in urothelial tumors. Whole transcriptional characterizations of the mouse bladder tumors revealed a significant overlap with human BC samples, and a predominant role for Ezh2 in the downregulation of gene expression programs. Importantly, we determined that in human superficial BC patients, the increased tumor recurrence and progression in these recurrences is associated with increased E2F and Ezh2 expression and Ezh2-mediated gene expression repression. Collectively, our studies provide a genetically defined model for human high-grade superficial BC and demonstrate the existence of an Rb-E2F-Ezh2 axis in bladder whose disruption can promote tumor development.
In vivo disruption of an Rb-E2F-Ezh2 signaling loop causes bladder cancer.
Specimen part, Disease, Treatment
View SamplesCdk4/6 inhibitors have shown to increase overall survival in hormone-positive breast tumors, but whether other solid tumors could respond to these inhibitors has not yet defined. Here we show that Palbociclib (a Cdk4/6 specific inhibitor in clinic use) treatment exerts antiproliferative effects in vivo using a bladder cancer cell lines.
CDK4/6 Inhibitor as a Novel Therapeutic Approach for Advanced Bladder Cancer Independently of <i>RB1</i> Status.
Specimen part, Cell line
View SamplesFloral organs, whose identity is determined by specific combinations of homeotic genes, originate from a group of undifferentiated cells called the floral meristem. In Arabidopsis, the homeotic gene AGAMOUS (AG) terminates meristem activity and promotes development of stamens and carpels.
Transcriptional program controlled by the floral homeotic gene AGAMOUS during early organogenesis.
No sample metadata fields
View SamplesA. thaliana plants were grown in 1/2 MS medium in the presence of carbenicillin (10 µg·mL-1) for 1 or 7 days and RNA from their roots extracted and sequenced in Illumina HiSeq 2000/5000 (2x50 bp). Overall design: Total RNA obtained from A. thaliana roots grown in the absence (mock) or presence of carbenicillin (10 µg·mL-1) for 1 or 7 days. Three replicas per experiment.
β-Lactam Antibiotics Modify Root Architecture and Indole Glucosinolate Metabolism in Arabidopsis thaliana.
Specimen part, Subject
View SamplesDiamond-Blackfan anemia (DBA) is characterized by anemia and cancer susceptibility, and is caused by mutations in ribosomal genes, including Rpl11. Here, we report that Rpl11-heterozygous embryos are not viable, and homozygous deletion of Rpl11 in adult mice results in death within a few weeks, accompanied by bone marrow aplasia and intestinal atrophy. Importantly, deletion of a single Rpl11 allele in adult mice results in anemia associated to decreased erythroid progenitors and defective erythroid maturation. These phenotypes are also present in mice transplanted with inducible heterozygous Rpl11 bone marrow, indicating a cell-autonomous role of RPL11 in erythropoiesis. Additionally, fibroblasts lacking one or both Rpl11 alleles show defective p53 activation upon ribosomal stress or DNA damage. Furthermore, fibroblasts and hematopoietic tissues from heterozygous Rpl11 mice present higher basal cMYC levels. Accordingly, heterozygous Rpl11 mice are highly susceptible to radiation-induced lymphomagenesis. We conclude that Rpl11-deficient mice recapitulate DBA disorder, including cancer predisposition. Overall design: RNAseq profiles of bone marrow hematopoietic progenitors cells from WT (Rpl11+/+:: Tg.UbC-CreERT2) and LOX (Rpl11+/lox::Tb.Ub-CreERT2) mice, n=4 independent animals per genotype
Partial Loss of Rpl11 in Adult Mice Recapitulates Diamond-Blackfan Anemia and Promotes Lymphomagenesis.
Sex, Age, Specimen part, Cell line, Subject
View SamplesTHO/TREX is a conserved nuclear complex that functions in mRNP biogenesis at the interface of transcription-RNA export with a key role in preventing transcription-associated genome instability.
Genome-wide function of THO/TREX in active genes prevents R-loop-dependent replication obstacles.
No sample metadata fields
View SamplesCulturing myotubes from skeletal muscle (SM) biopsies enables investigating transcriptional defects and assaying therapeutic strategies. This study compares the transcriptome of aneurally cultured human SM cells versus that of tissue biopsies.
Comparative gene expression profiling between human cultured myotubes and skeletal muscle tissue.
Sex, Specimen part
View SamplesWe profiled total liver mRNA of WT and p21KO mice that were fed ad libitum or fasted for 24 hours Overall design: 2-3 mice of each genotype were either fed or fasted for 24 hours, sacrificed and total mRNA was extracted from liver (we mapped >12M reads per sample)
p21<sup>Cip1</sup> plays a critical role in the physiological adaptation to fasting through activation of PPARα.
Specimen part, Subject
View SamplesObesity is a chronic, complex and multifactorial disease that has reached pandemia levels and is becoming a serious health problem. Intestinal microbiota is considered a main factor that affects body weight and fat mass, which points toward a critical role in the development of obesity. In this sense, probiotic bacteria might modulate the intestinal microbiota and the mucosal-associated lymphoid tissue. The aim of this study was to investigate the effects of L. paracasei, L. rhamnosus and B. breve feeding on the intestinal mucosa gene expression in a genetic animal model of obesity.
Adamdec1, Ednrb and Ptgs1/Cox1, inflammation genes upregulated in the intestinal mucosa of obese rats, are downregulated by three probiotic strains.
Specimen part
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