We conditionally inactivated mouse Cdx2, a dominant regulator of intestinal development, and mapped its genome occupancy in adult intestinal villi. Although homeotic transformation, observed in Cdx2-null embryos, was absent in mutant adults, gene expression and cell morphology were vitally compromised. Lethality was accelerated in mice lacking both Cdx2 and its homolog Cdx1, with exaggeration of defects in crypt cell replication and enterocyte differentiation. Cdx2 occupancy correlated with hundreds of transcripts that fell but not with equal numbers that rose with Cdx loss, indicating a predominantly activating role at intestinal cis-regulatory regions. Integrated consideration of a mutant phenotype and cistrome hence reveals the continued and distinct requirement in adults of a master developmental regulator that activates tissue-specific genes.
Essential and redundant functions of caudal family proteins in activating adult intestinal genes.
Specimen part
View SamplesTranscription factor Foxq1 controls mucin gene expression and granule content in mouse stomach surface mucous cells
Transcription factor foxq1 controls mucin gene expression and granule content in mouse stomach surface mucous cells.
No sample metadata fields
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DOT1L-mediated H3K79 methylation in chromatin is dispensable for Wnt pathway-specific and other intestinal epithelial functions.
Specimen part
View SamplesWe used microarrays to detail the differentail gene expression between intestinal Lgr5(hi) stem cells and differentiated cells
DOT1L-mediated H3K79 methylation in chromatin is dispensable for Wnt pathway-specific and other intestinal epithelial functions.
Specimen part
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Intestinal master transcription factor CDX2 controls chromatin access for partner transcription factor binding.
Specimen part
View SamplesWe established whether partner transcription factor binding, chromatin structure, or gene expression is compromised upon loss of partner factors cdx2 or hnf4a in mouse intestinal villi
Intestinal master transcription factor CDX2 controls chromatin access for partner transcription factor binding.
Specimen part
View SamplesTo determine whether the intestine-restricted transcription factor (TF) CDX2 functionally interacts with the endoderm-wide TF HNF4A, we crossed tissue-specific conditional Cdx2 and Hnf4a knockout mice to generate compound mutant mice. We used RNA-sequencing to profile gene expression changes in compound mutant mice compared to control mice. The compound mutant mice had a significantly worse phenotype than either single mutant, and gene expression was significantly perturbed in compound mutants compared to control mice. Overall design: Total RNA isolated from control and compound mutant (Hnf4a-del;Cdx2-del) jejunal mouse intestinal epithelium was prepared for sequencing using the TruSeq RNA Sample Preparation Kit (Illumina) according to the manufacturer''s instructions. 75-base-pair single-end reads were sequenced on an Illumina NextSeq 500 instrument. The data include 2 independent biological replicates per genotype.
Transcription factors GATA4 and HNF4A control distinct aspects of intestinal homeostasis in conjunction with transcription factor CDX2.
No sample metadata fields
View SamplesColorectal cancer (CRC) remains the leading cause of cancer-related death in the world. Aspirin (ASA) and curcumin (CUR) are widely investigated chemopreventive candidates for CRC. However, the precise mechanisms of their action and their combinatorial effects have not been evaluated. The purpose of the present study was to determine the effect of ASA, CUR, and their combination in azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colitis-accelerated colorectal cancer (CAC). We also aimed to characterize the differential gene expression profiles in AOM/DSS-induced tumors as well as in tumors modulated by ASA and CUR using RNA-seq. Diets supplemented with 0.02% ASA, 2% CUR or 0.01% ASA + 1% CUR were given to mice from 1 week prior to the AOM injection until the experiment was terminated 22 weeks after AOM initiation. Our results showed that CUR had a superior inhibitory effect in colon tumorigenesis compared to that of ASA. The combination of ASA and CUR at a lower dose exhibited similar efficacy to that of a higher dose of CUR at 2%. RNA isolated from colonic tissue from the control group and from tumor samples from the experimental groups was subjected to RNA-seq. Transcriptomic analysis suggested that the low-dose combination of ASA and CUR modulated larger gene sets than the single treatment. These differentially expressed genes were situated in several canonical pathways important in the inflammatory network and liver metastasis in CAC. We identified a small subset of genes as potential molecular targets involved in the preventive action of the combination of ASA and CUR. Taken together, the current results provide the first evidence in support of the chemopreventive effect of a low-dose combination of ASA and CUR in CAC. Moreover, the transcriptional profile obtained in our study may provide a framework for identifying the mechanisms underlying the carcinogenesis process from normal colonic tissue to tumor development as well as the cancer inhibitory effects and potential molecular targets of ASA and CUR. Overall design: 10 RNA samples (5 experimental groups with duplicates) were sequenced using Illumina NextSeq 500 instrument.
Mechanisms of colitis-accelerated colon carcinogenesis and its prevention with the combination of aspirin and curcumin: Transcriptomic analysis using RNA-seq.
Specimen part, Treatment, Subject
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Broadly permissive intestinal chromatin underlies lateral inhibition and cell plasticity.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
YY1 is indispensable for Lgr5+ intestinal stem cell renewal.
Specimen part
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