Colon 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.
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View SamplesInduction of germline-competent pluripotent stem cells from mouse fibroblasts has been achieved by the ectopic expression of four genes (Oct3/4, Sox2, c-Myc and Klf4). If this method can be applied to humans for the generation of personalized human pluripotent stem cells, it would greatly facilitate the therapeutic application of stem cells by avoiding the problem of immune rejection by the recipient associated with allograft transplants. Here we show that the ectopic expression of the same four genes in human neonatal skin derived cells is sufficient to induce pluripotent stem cells indistinguishable from human embryonic stem cells in morphology, gene expression, DNA methylation, teratoma formation and long term self-renewal ability. Extensive analysis of colonies generated by ectopic expression of these four genes indicates the presence of considerable heterogeneity in the induced colonies. These results provide a new finding to generate human induced pluripotent stem cells from postnatal somatic tissues.
Heterogeneity of pluripotent marker gene expression in colonies generated in human iPS cell induction culture.
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View SamplesPulmonary alveoli are complex architectural units thought to undergo endogenous or pharmacologically induced programs of regeneration and degeneration. To study the molecular mechanism of alveoli loss mice were calorie restricted at different timepoints. Lungs were harvested and processed for RNA extraction.
Calorie-related rapid onset of alveolar loss, regeneration, and changes in mouse lung gene expression.
Time
View SamplesIt has been shown that dexamethasone (Dex) impairs the normal lung septation that occurs in the early postnatal period. Treatment with retinoic acid (ATRA) abrogates the effects of Dex. To understand the molecular basis for the Dex indiced inhibition of the formation of the alveoli and the ability of ATRA to prevent the inhibition of septation, gene expression was analyzed in 4-day old mice treated with diluent (control), Dex-treated and ATRA+Dex-treated.
DNA microarray analysis of neonatal mouse lung connects regulation of KDR with dexamethasone-induced inhibition of alveolar formation.
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View SamplesUterine double conditional inactivation of Smad2 and Smad3 in mice results in endometrial dysregulation, infertility, and uterine cancer. Smad2/3 cKO mice demonstrate abnormal expression of genes involved in inflammation, cell-cycle checkpoint, migration, steroid biosynthesis, and SMAD1/5-driven genes. We performed RNA-sequencing to identify the gene expression differences between the uterine epithelium of control and Smad2/3 cKO. To control for estrous cycle variations, the uterine epithelium was collected from mice at 0.5 dpc. Global gene expression profiles of Smad2/3 cKO versus control mice was analyzed. Our RNA sequencing analysis was performed at 6 weeks of life and already showed significant differences in migratory (Agr2,Slit2) and inflammatory (Ccl20, Crispld2) markers between Smad2/3 cKO and control mice. Overall design: Two group comparison: uterine epithelium of control and Smad2/3 cKO mice. We generated a conditional knockout of Smad2/3 in the uterus and demonstrated that Smad2/3 plays a critical role in the endometrium, with disruption resulting in pubertal-onset uterine hyperplasia and ultimately fatal uterine cancer.
Uterine double-conditional inactivation of <i>Smad2</i> and <i>Smad3</i> in mice causes endometrial dysregulation, infertility, and uterine cancer.
Specimen part, Subject
View SamplesUnderstanding the mechanisms by which cells respond to chemotherapeutics is key to identifying means to improve therapy effiicacy while reducing systemic toxicity of these widely used classes of drugs. While determining the role of NRF2-GSH and ER stress in cells exposed to alkylating compounds such as methyl-methanesulfonate (MMS), we asked if these pathways could also be a general cell damage response relevant to other clinically used chemotherapeutics or if it is an alkylation specific response. With this intent, we performed RNA sequencing of MDA-MB231 breast cancer and U2OS osteosarcoma cells lines treated for 8 hours with a topoisomerase II inhibitor etoposide (20 µM), the antimitotic beta-tubulin-interacting drug paclitaxel (0.2 µM), doxorubicin (1 µM) and compared to MMS (40 µg/mL) treated cells. Doses represent IC50 level after 72 hours exposure. We observed that even though non-alkylating drugs, especially etoposide, caused an increase in the mRNA expression of some NRF2 and ER stress signaling markers, the number and magnitude of upregulation of genes markers in either pathway was more pronounced in alkylation treatments compared to other drugs. This indicates that alterations in NRF2 and ER stress pathways could be more likely associated with differential sensitivity to alkylating chemotherapies. Overall design: MDA-MB231 breast cancer and U2OS osteosarcoma cells lines were treated with the 72 h IC50 dose of etoposide (20 µM), paclitaxel (0.2 µM), doxorubicin (1 µM) or MMS (40 µg/mL) for 8 h, and RNA was extracted and analyzed.
Alkylating Agent-Induced NRF2 Blocks Endoplasmic Reticulum Stress-Mediated Apoptosis via Control of Glutathione Pools and Protein Thiol Homeostasis.
Specimen part, Cell line, Treatment, Subject
View SamplesUlcerative colitis (UC) is a chronic inflammatory disease of the colon with preiods of active disease followed by remission.
Transcriptional analysis of the intestinal mucosa of patients with ulcerative colitis in remission reveals lasting epithelial cell alterations.
Sex, Age, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Depletion of DNMT1 in differentiated human cells highlights key classes of sensitive genes and an interplay with polycomb repression.
Sex, Specimen part, Time
View SamplesDNA methylation plays a vital role in the cell, but loss-of-function mutations of the maintenance methyltransferase DNMT1 in normal human cells are lethal, precluding target identification, and existing hypomorphic lines are tumour cells. We generated instead a hypomorphic series in normal hTERT-immortalised fibroblasts using stably integrated short hairpin RNA. Approx 2/3 of sites showed demethylation as expected, with 1/3 showing hypermethylation, and targets were shared between the three independently-derived lines. Enrichment analysis indicated significant losses at promoters and gene bodies with four gene classes most affected: 1)protocadherins, which are key to neural cell identity; 2)genes involved in fat homeostasis/body mass determination; 3)olfactory receptors and 4) cancer/testis antigen (CTA) genes. Overall effects on transcription were relatively small in these fibroblasts, but CTA genes showed robust derepression. Comparison with siRNA-treated cells indicated that shRNA lines show substantial remethylation over time. Regions showing persistent hypomethylation in the shRNA lines were associated with polycomb repression, and were derepressed on addition of an EZH2 inhibitor. Persistent hypermethylation in shRNA lines was in contrast associated with poised promoters. Our results suggest polycomb marking blocks remethylation and indicate the sensitivity of key neural, adipose, and cancer-associated genes to chronic depletion of maintenance methylation activity.
Depletion of DNMT1 in differentiated human cells highlights key classes of sensitive genes and an interplay with polycomb repression.
Sex, Specimen part, Time
View SamplesCrohn's Disease (CD) is a chronic inflammatory disease of the intestinal tract.
Identification of inflammatory mediators in patients with Crohn's disease unresponsive to anti-TNFα therapy.
Sex, Age, Specimen part, Subject
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