Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA270994 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Gene expression profiling of proximal versus distal mouse colon during AOM/DSS-induced colitis-associated carcinogenesis.
| PRJNA271582 | ENA
Project description:To describe the protein profile in hippocampus, colon and ileum tissue’ changing after the old faeces transplants, we adopted a quantitative label free proteomics approach.
2021-09-09 | PXD016432 | Pride
Project description:<p>The incidence of intestinal diseases increases with age, but the regulators of gut aging and the molecules linking gut aging and diseases remain largely unknown. By profiling the transcriptome, proteome, phosphoproteome and metabolome of 104 <em>Macaca fascicularis</em> large intestinal tissues, we unveiled asynchronous aging within the proximal and distal colon. The levels of many gene products, phosphosites and metabolites changed with age in a location- and sex-dependent manner, and many of these changes occurred at distinct rates or even in opposite directions at different locations. Assessment of 60 age-related molecules (genes, phosphosites, metabolites) across<em> C. elegans</em>, mice, and cell lines identified 32 crucial regulators of gut atrophy and barrier integrity. Notably, we found that tryptophan metabolism via the kynurenine and serotonin (5-HT) pathways was more active in the proximal and distal colon, respectively. In a mouse colitis model, reducing 5-HT production with a Tph1 inhibitor alleviated distal but not proximal colitis, while adding 5-HT aggravated distal symptoms, indicating that distal colitis is more sensitive to 5-HT fluctuations. Moreover, we identified 24 proteins, particularly HPX, that potentially link gut aging to colorectal cancer (CRC). High levels of HPX in CRC predicted poor prognosis in patients older than 50 yr but not in younger patients, suggesting that an age-linked HPX increase in the gut may contribute to CRC progression. Collectively, this work reveals the heterogeneity of large intestinal aging in non-human primates and offers promising targets for preventing gut aging and diseases.</p>
2023-12-14 | MTBLS7612 | MetaboLights
Project description:Lcn2 is involved in host defense against pathogens, but the function in intestinal mucosal immunity and inflammation remains largely unknown. Genetic ablation of Lcn2 results in early-onset colitis and spontaneous emergence of right-sided colonic tumors in the setting of IL-10 deficiency (Lcn2-/-;IL10-/- mice). To address whether inflammation or other mechanisms drives the site-specific tumor locations gene expression analyses in proximal versus distal colons of Lcn2-/- IL10-/- mice were performed. Differential expression between distal colon versus cecum and proximal colon samples were analyses using Affymetrix MoGene 2.0 ST arrays on formalin-fixed, paraffin-embedded tissue sections of Lcn2-/-; IL10-/-mice.
2016-03-30 | E-MTAB-4583 | biostudies-arrayexpress
Project description:Goal: Since disease susceptibility of the intestine exhibits an anatomical bias, we propose that the chromatin landscape, especially the site-specific epigenetic differences in histone modification patterns throughout the longitudinal axis, contributes to a differential response to chemoprotective agents. Method: We assessed the chromatin structure associated with gene expression profiles in the rat proximal and distal colon by globally correlating chromatin immunoprecipitation next-generation sequencing analysis (ChIP-Seq) with mRNA transcription (RNA-Seq) data. Crypts were isolated from the proximal and distal colonic regions from rats maintained on a semi-purified diet, and mRNA gene expression profiles were generated using RNA-Seq. The remaining isolated crypts were paraformaldehyde-crosslinked and chromatin immunoprecipitated using antibodies against H3K4me3, H3K9me3, and RNA Polymerase II. Results/Conclusion: Globally, RNA-Seq results indicated that 9,866 genes were actively expressed, of which 540 genes were differentially expressed between the proximal and distal colon. With regard to differentially expressed genes, a high correlation was observed between H3K4me3-Seq and RNA-Seq data, with 96% of the canonical pathways being similarly affected in the H3K4me3-Seq and RNA-Seq data sets. Gene ontology analysis indicated that colonic crypt location significantly impacted both chromatin and transcriptional regulation of genes involved in cell transformation, lipid metabolism, lymphatic development and immune cell trafficking. Gene function analysis indicated that the PI3-Kinase signaling pathway was regulated in a site-specific manner, e.g., pathway proto-oncogenes, c-Jun, c-Fos and ATF, were up-regulated in the distal colon. Middle and long non-coding RNAs (lncRNAs) were also detected in the colon, including select lncRNAs formerly only detected in the rat nervous system. In summary, distinct combinatorial patterns of histone modifications exist in the proximal versus distal colon. These site-specific differences may explain the differential effects of chemoprotective agents on cell transformation in the ascending (proximal) and descending (distal) colon. Examination of mRNA profiles and 2 different histone modifications (H3K4me3 and H3K9me3) in 2 tissue types (proximal and distal colon).
2013-08-01 | E-GEOD-49389 | biostudies-arrayexpress
Project description:Analysis of gene expression in proximal versus distal part of the mouse large intestine.
2015-01-01 | GSE64423 | GEO
Project description:PURPOSE: To provide a detailed gene expression profile of the normal postnatal mouse cornea. METHODS: Serial analysis of gene expression (SAGE) was performed on postnatal day (PN)9 and adult mouse (6 week) total corneas. The expression of selected genes was analyzed by in situ hybridization. RESULTS: A total of 64,272 PN9 and 62,206 adult tags were sequenced. Mouse corneal transcriptomes are composed of at least 19,544 and 18,509 unique mRNAs, respectively. One third of the unique tags were expressed at both stages, whereas a third was identified exclusively in PN9 or adult corneas. Three hundred thirty-four PN9 and 339 adult tags were enriched more than fivefold over other published nonocular libraries. Abundant transcripts were associated with metabolic functions, redox activities, and barrier integrity. Three members of the Ly-6/uPAR family whose functions are unknown in the cornea constitute more than 1% of the total mRNA. Aquaporin 5, epithelial membrane protein and glutathione-S-transferase (GST) omega-1, and GST alpha-4 mRNAs were preferentially expressed in distinct corneal epithelial layers, providing new markers for stratification. More than 200 tags were differentially expressed, of which 25 mediate transcription. CONCLUSIONS: In addition to providing a detailed profile of expressed genes in the PN9 and mature mouse cornea, the present SAGE data demonstrate dynamic changes in gene expression after eye opening and provide new probes for exploring corneal epithelial cell stratification, development, and function and for exploring the intricate relationship between programmed and environmentally induced gene expression in the cornea. Keywords: other
2004-01-02 | GSE887 | GEO
Project description:Analysis of gene expression in proximal versus distal part of the mouse large intestine. Three (3) animals (biological replicates) were used to isolate tissue from proximal and distal areas of the large intestine.
2015-01-01 | E-GEOD-64423 | biostudies-arrayexpress
Project description:It is not known why cancers arising in anatomically distinct locations but within the same tissue type can exhibit stark differences in molecular, pathological and clinical features. Cancers arising in proximal and distal sites of the colon are emblematic of these above differences as the proximal and distal colon cancers harbor differences in key molecular features, with BRAFV600E oncogene predominantly occurring in proximal colon cancers in the context of the increased promoter DNA methylation phenotype (CIMP-high), while distal colon cancers lack these molecular features. We determined the molecular basis of tissue-location specificity of driver mutations using normal mouse derived organoid models for colon cancer initiation. We show that the homeobox transcription factor, Cdx2, which is downregulated by DNA methylation in proximal colon cancers, plays distinct roles in regulating stem cell and differentiation in proximal compared to distal colon stem cells. Loss of Cdx2 altered the differentiation and stem cell programs and result in transformation by BRAFV600E specifically in the proximal but not distal colon stem cells. Analyses of RNA expression and Cdx2-binding to target genomic regions revealed that Cdx2 was a key effector of the transcriptional response to differentiation cues in proximal colon cells. This proximal colon-specific transcriptional program concurrently is tumor suppressive, and its loss sufficiently creates permissive state for oncogenic-BRAF mutations. The transcriptional program associated with Cdx2 loss in mouse proximal organoids matches that of human proximal colon cancers with downregulated CDX2 expression due to epigenetic silencing. Our analyses reveal that developmental and lineage-restricted transcription factors maintain tissue-location specific transcriptional programs which create critical dependencies for tumor initiation.
2023-12-12 | GSE218480 | GEO
Project description:It is not known why cancers arising in anatomically distinct locations but within the same tissue type can exhibit stark differences in molecular, pathological and clinical features. Cancers arising in proximal and distal sites of the colon are emblematic of these above differences as the proximal and distal colon cancers harbor differences in key molecular features, with BRAFV600E oncogene predominantly occurring in proximal colon cancers in the context of the increased promoter DNA methylation phenotype (CIMP-high), while distal colon cancers lack these molecular features. We determined the molecular basis of tissue-location specificity of driver mutations using normal mouse derived organoid models for colon cancer initiation. We show that the homeobox transcription factor, Cdx2, which is downregulated by DNA methylation in proximal colon cancers, plays distinct roles in regulating stem cell and differentiation in proximal compared to distal colon stem cells. Loss of Cdx2 altered the differentiation and stem cell programs and result in transformation by BRAFV600E specifically in the proximal but not distal colon stem cells. Analyses of RNA expression and Cdx2-binding to target genomic regions revealed that Cdx2 was a key effector of the transcriptional response to differentiation cues in proximal colon cells. This proximal colon-specific transcriptional program concurrently is tumor suppressive, and its loss sufficiently creates permissive state for oncogenic-BRAF mutations. The transcriptional program associated with Cdx2 loss in mouse proximal organoids matches that of human proximal colon cancers with downregulated CDX2 expression due to epigenetic silencing. Our analyses reveal that developmental and lineage-restricted transcription factors maintain tissue-location specific transcriptional programs which create critical dependencies for tumor initiation.
2023-12-12 | GSE218479 | GEO