Most human cancers present hyperactivated sumoylation, and cancer cell lines are usually highly sensitive to the lack of it, supporting potential application of sumoylation chemical inhibitors in cancer therapy. Here, we explored the impact of hyposumoylation (Ubc9 haploinsufficiency) on cancer development in mice using Apc loss-driven intestinal tumorigenesis model.
An unanticipated tumor-suppressive role of the SUMO pathway in the intestine unveiled by Ubc9 haploinsufficiency.
Specimen part
View SamplesThe Lgr5+ intestinal stem cell, Paneth and transit-amplifying cell compartment constitute the intestinal crypt which is the constant source of differentiated epithelial cells that replenish the intestinal villi ensuring organ maintenance and regeneration. The Lgr5+ crypt-based columnar (CBC) cells have been identified as the intestinal stem cells (ISCs) and, importantly, as cells-of-origin of intestinal cancer.
An unanticipated tumor-suppressive role of the SUMO pathway in the intestine unveiled by Ubc9 haploinsufficiency.
Specimen part
View SamplesComparative RNA profiling between tumor cells and their secreted extracellular vesicles. Results revealed enrichment in genes involved in cellular migration and metastasis in extracellular vesicles, in agreement with their role as mediators of tumor progression.
In Vivo imaging reveals extracellular vesicle-mediated phenocopying of metastatic behavior.
Cell line
View SamplesBackground: Obesity is a risk factor for breast cancer in postmenopausal women and is associated with decreased survival and less favorable clinical characteristics such as greater tumor burden, higher grade, and poor prognosis, regardless of menopausal status. Despite the negative impact of obesity on clinical outcome, molecular mechanisms through which excess adiposity influences breast cancer etiology are not well-defined.
Effect of obesity on molecular characteristics of invasive breast tumors: gene expression analysis in a large cohort of female patients.
Disease stage
View SamplesLgr5+ stem cells reside at crypt bottoms of the small and large intestine. Small intestinal Paneth cells supply Wnt3, EGF and Notch signals to neighboring Lgr5+ stem cells. While the colon lacks Paneth cells, Deep Crypt Secretory (DCS) cells are intermingled with Lgr5+ stem cells at crypt bottoms. Here, we report Reg4 as a marker of DCS cells. To investigate a niche function, we eliminated DCS cells using the diphtheria-toxin receptor gene knocked into the murine Reg4 locus. Ablation of DCS cells results in loss of stem cells from colonic crypts and disrupts gut homeostasis and colon mini-gut formation. In agreement, sorted Reg4+ DCS cells promote organoid formation of single Lgr5+ colon stem cells. Stem cells are forced to generate DCS cells in vitro by combined Notch inhibition and Wnt activation. We conclude that Reg4+ DCS cells serve as Paneth cell equivalents in the colon crypt niche. Overall design: To define a global gene expression signature of DCS cells, we performed RNA-sequencing (RNA-seq) of sorted Reg4-dsRed+ and Lgr5-GFP+ cells from colonic epithelium. Sorting and RNA-seq library preparation was performed twice, to obtain a biological replicate.
Reg4+ deep crypt secretory cells function as epithelial niche for Lgr5+ stem cells in colon.
No sample metadata fields
View SamplesPurpose: identifying genes responding to insulin stimulation in S2R+ cells through whole transcriptome RNA-seq analyses Methods: Total RNA was extracted from S2R+ cells using TRIzol® reagent (Invitrogen). After assessing RNA quality with an Agilent Bioanalyzer, libraries were constructed with Illumina TruSeq mRNA Library Prep Kit , libraries were sequenced using an Illumina HiSeq 4000 at the Columbia Genome Center (http://systemsbiology.columbia.edu/genome-center). Results: Using an time series data analysis workflow incorporating polynormials , we identified 1254 temproally differentially expressed genes responding to insulin stimulation in the S2R+ cells. Overall design: the pre-starved S2R+ cells ( with serum free medium) were stimulated with insulin; triplicate samples were collected at basline and every 20minutes time interval up to three hours; transcriptome profiling
Interspecies analysis of MYC targets identifies tRNA synthetases as mediators of growth and survival in MYC-overexpressing cells.
Specimen part, Treatment, Subject, Time
View SamplesUremic media calcification is not only driven by systemic factors such as hyperphosphatemia, but also crticially dependent on vascular smooth muscle cells per se. We hypothesized that the different developmental origins of vscular smooth muscle cells might lead to a heterogeneous susceptibility to develop media calcification.
Heterogeneous susceptibility for uraemic media calcification and concomitant inflammation within the arterial tree.
Specimen part
View SamplesPurpose: Aerobic capacity is a strong predictor of cardiovascular mortality. To determine the relationship between inborn aerobic capacity and soleus gene expression we examined genome-wide gene expression in soleus muscle of rats artificially selected for high and low running capacity (HCR and LCR, respectively) over 16 generations. The artificial selection of LCR caused accumulation of risk factors of cardiovascular disease similar to the metabolic syndrome seen in man, whereas HCR had markedly better cardiac function. We also studied alterations in gene expression in response to exercise training in the two groups, since accumulating evidence indicates that exercise has profound beneficial effects on the metabolic syndrome.
Gene expression profiling of skeletal muscle in exercise-trained and sedentary rats with inborn high and low VO2max.
No sample metadata fields
View SamplesAerobic capacity is a strong predictor of cardiovascular mortality. To determine the relationship between aerobic capacity and cardiac gene expression we examined genome-wide gene expression in hearts of rats artificially selected for high- and low running capacity (HCR and LCR, respectively) over 16 generations. HCR were born with an athletic phenotype, whereas LCR exhibited features of the metabolic syndrome.
Aerobic capacity-dependent differences in cardiac gene expression.
Sex
View SamplesThese patients proved resistant to docetaxel treatment, exhibiting residual tumor of 25% or greater remaining volume.
Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer.
No sample metadata fields
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