DNA methylation, at CpG islands and promoters, is often inversely correlated with gene expression.
The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores.
Specimen part
View SamplesPluripotent stem cells (PSCs) exist in multiple stable states, each with specific cellular properties and molecular signatures. The process by which pluripotency is either maintained or destabilized to initiate specific developmental programs is poorly understood. We have developed a model to predict stabilized PSC gene regulatory network (GRN) states in response to combinations of input signals. While previous attempts to model PSC fate have been limited to static cell compositions, our approach enables simulations of dynamic heterogeneity by combining an Asynchronous Boolean Simulation (ABS) strategy with simulated single cell fate transitions using a Strongly Connected Components (SCCs). This computational framework was applied to a reverse-engineered and curated core GRN for mouse embryonic stem cells (mESCs) to simulate responses to LIF, Wnt/ß-catenin, FGF/ERK, BMP4, and Activin A/Nodal pathway activation. For these input signals, our simulations exhibit strong predictive power for gene expression patterns, cell population composition, and nodes controlling cell fate transitions. The model predictions extend into early PSC differentiation, demonstrating, for example, that a Cdx2-high/Oct4-low state can be efficiently generated from mESCs residing in a naïve and signal-receptive state sustained by combinations of signaling activators and inhibitors. Overall design: Examination of perturbed PSCs versus control PSCs and mesoderm progenitors Mouse pluripotent stem cells were grown on tissue culture plates for two days in serum-containing, feeder free medium supplemented with the following cytokines/small molecules: 2i = CHIR99021 (Reagents Direct 27-H76 – 3µM) & PD0325901 (Reagents Direct 39-C68 – 1µM) Jaki = JAK inhibitor (EMD Millipore 420097 – 2.0µM) BMP = BMP4 (R&D Systems 314-BP-010 – 10ng/ml) Alk5i = ALK5 inhibitor II (Cedarlane ALX-270-445 - 10µM)
Modeling signaling-dependent pluripotency with Boolean logic to predict cell fate transitions.
Cell line, Treatment, Subject, Time
View SamplesColon cancer invade to depper layer and the expression of major molecules at cancer front change. But the screening of expression changing at cancer front has not be adequtely clarified.
Microarray Analysis of Gene Expression at the Tumor Front of Colon Cancer.
No sample metadata fields
View SamplesIn the vertebrate retina, the Otx2 transcription factor plays a crucial role in the cell fate determination of both rod and cone photoreceptors. Otx2 conditional knockout (CKO) mice exhibited a total absence of rods and cones in the retina due to their cell fate conversion to amacrine-like cells. In order to investigate the entire transcriptome regulated by Otx2 in the developing retina, we performed microarray analysis on the Otx2 CKO retina.
Analysis of transcriptional regulatory pathways of photoreceptor genes by expression profiling of the Otx2-deficient retina.
Specimen part, Time
View SamplesCellular differentiation is regulated through activation and repression of defined transcription factors. A hallmark of differentiation is a pronounced change in cell shape, which is determined by dynamics of the actin cytoskeleton. In de-differentiated fat (DFAT) cells and 3T3-L1 cells, we showed that treatment with the ROCK inhibitor Y-27632, by inducing remodeling of the actin cytoskelton, causes adipocyte differentiation. In addition, we found that depletion of MKL1, an actin binding transcriptional coactivator, elicits adipogenesis.
Regulation of MKL1 via actin cytoskeleton dynamics drives adipocyte differentiation.
Specimen part
View SamplesWe performed RNA sequencing on melanopsin deleted retinas (Opn4-DTA/DTA) to determine potential cues involved in instructing cone photoreceptor positioning Overall design: RNAseq of whole P8 retinal extracts from wild-type littermate vs. Opn4DTA/DTA mice
Melanopsin Retinal Ganglion Cells Regulate Cone Photoreceptor Lamination in the Mouse Retina.
Specimen part, Subject
View SamplesUnder hypoxic conditions, nitroimidazole compounds accumulate in cells in their reduced form and have oxygen-mimetic effects, serving as markers of hypoxia and radiosensitizers. The full potential of their bioreductive metabolism, including cytotoxicity for cancer stem cells, has not been sufficiently explored, however. Here we investigated the changes in gene expression induced by treatment with 2-nitroimidazole doranidazole in murine glioma stem cells, under normoxic or hypoxic conditions.
2-Nitroimidazoles induce mitochondrial stress and ferroptosis in glioma stem cells residing in a hypoxic niche.
Specimen part
View SamplesGene expression data from mouse organs after hydroxypropyl--cyclodextrin injection
Hydroxypropyl-β-cyclodextrin spikes local inflammation that induces Th2 cell and T follicular helper cell responses to the coadministered antigen.
Sex, Specimen part
View SamplesWe investigated the RNA expression levels of NF-kB ligands and their receptors in epithelial cancer cells and cancer-associated fibroblasts (CAFs) from KPC tumors Overall design: We analysed 8 samples total (2 biological replicates. Each replicate with 2 conditions: DAPI- sorted cells (all live cells) and DAPI-CD45-CD31-EpCAM-PDPN+ sorted cells (CAFs). Each condition with 2 technical replicates.
IL1-Induced JAK/STAT Signaling Is Antagonized by TGFβ to Shape CAF Heterogeneity in Pancreatic Ductal Adenocarcinoma.
Specimen part, Subject
View SamplesMen are at an increased risk of dying from heart failure caused by inflammatory heart diseases such as atherosclerosis, myocarditis and dilated cardiomyopathy (DCM). We previously showed that macrophages in the spleen are phenotypically distinct in male compared to female mice at 12 hours (h) after infection. This innate immune profile mirrors and predicts the cardiac immune response during acute myocarditis.
The innate immune response to coxsackievirus B3 predicts progression to cardiovascular disease and heart failure in male mice.
Sex, Specimen part
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