Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA388453 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5628653.fastq.gz | Fastqsanger.gz | |||
| SRR5628654.fastq.gz | Fastqsanger.gz | |||
| SRR5628655.fastq.gz | Fastqsanger.gz | |||
| SRR5628656.fastq.gz | Fastqsanger.gz | |||
| SRR5628657.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:AP4 regulates stem and Paneth cell homeostasis and promotes adenoma initiation in the intestine (adenoma)
| PRJNA388457 | ENA
Project description:Recently, three-dimensional small intestinal organoids (enteroids) have been developed from cultures of intestinal stem cells which differentiate in vitro to generate all the differentiated epithelial cell types associated with the intestine and mimic the structural properties of the intestine observed in vivo. Small-molecule drug treatment can skew organoid epithelial cell differentiation towards particular lineages, and these skewed enteroids may provide useful tools to study specific epithelial cell populations, such as goblet and Paneth cells. However, the use and characterisation of enteroid models has not yet been fully explored, such that the extent to which differentiated epithelial cell populations in these skewed enteroids represent their in vivo counterparts is not fully understood. In this study, we have performed label-free quantitative proteomics to determine whether skewing murine enteroid cultures towards the goblet or Paneth cell lineages results in changes in abundance of proteins associated with these cell lineages in vivo. Our data confirm that skewed enteroids recapitulate important features of the in vivo gut environment, confirming that they can serve as useful models for the investigation of normal and disease processes in the intestine. Furthermore, by comparison of our mass spectrometry data with histology data contained within the Human Protein Atlas, we identify putative novel markers for goblet and Paneth cells.
2019-01-11 | PXD005006 | Pride
Project description:Lgr5+ 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.
2016-10-05 | GSE63256 | GEO
Project description:Human intestinal epithelial organoids (IEO) culture models are rapidly emerging as novel experimental tools to investigate fundamental aspects of intestinal epithelial (patho)physiology. Cellular source and culture protocols vary between different IEO models and reliable markers for their characterization/validation are currently limited. Here, we provide the following reference datasets of transcriptomic profiling by RNA-sequencing: Purified intestinal epithelial cells (EpCAM+) from paediatric ileum and colon, Intestinal organoid cultures from paediatric ileum and colon, Purified intestinal epithelial cells (EpCAM+) from foetal small intestine and foetal large intestine, Intestinal organoid cultures from foetal small intestine and foetal large intestine, Intestinal organoid cultures derived from induced pluripotent stem cells.<br> Complementary data from methylation profiling on the same samples have been deposited at ArrayExpress under accession number E-MTAB-4957 ( https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-4957 ).</br>
2018-01-20 | E-MTAB-5015 | biostudies-arrayexpress
Project description:Differentiation and specialisation of epithelial cells in the small intestine is regulated in two ways. First, there is differentiation along the crypt-villus axis of the intestinal stem cells into absorptive enterocytes, Paneth, goblet, tuft, enteroendocrine or M-cells, which is mainly regulated by WNT. Second, there is specialization along the cephalocaudal axis with different absorptive and digestive functions in duodenum, jejunum and ileum that is controlled by several transcription factors such as GATA4. However, so far it is unknown whether location-specific functional properties are intrinsically programmed within stem cells or if continuous signalling from mesenchymal cells is necessary to maintain the location-specific identity of the small intestine. By using the pure epithelial organoid technique, we show that region-specific gene expression profiles are conserved throughout long-term cultures of both mouse and human intestinal stem cells and correlated with differential Gata4 expression. Furthermore, the human organoid culture system demonstrates that Gata4-regulated gene expression is only allowed in absence of WNT signalling. These data show that location-specific function is intrinsically programmed in the adult stem cells of the small intestine and that their differentiation fate is independent of location-specific extracellular signals. In light of the potential future clinical application of small intestine-derived organoids, our data imply that it is important to generate GATA4-positive and GATA4-negative cultures to regenerate all essential functions of the small intestine. RNA sequencing of intestinal crypts, villi and cultured organoids derived from mouse duodenum, jejunum and ileum
2014-01-07 | E-GEOD-53297 | biostudies-arrayexpress
Project description:Aberrant activation of the canonical Wnt pathway underlines the development and growth of intestinal tumors. The Apc-min (multiple intestinal neoplasia) mouse strain carries a single nucleotide mutation in one allele of the Apc tumor suppressor gene. Random deactivation of the second allele occurs during the life and results in the formation of multiple adenomas in the small intestine with occasional colonic occurence. The Defa6 promoter is active in adult small intestinal Paneth cells and its activation has been observed also in human colonic adenomas. To investigate the nature of Defa6+ colon adenoma cells, we used the Apc-min Rosa26-tdTomato Defa6-iCre mouse strain. In this strain, cells with an active Defa6 promoter are marked by expression of a red fluorescent protein (tdTomato). We performed gene expression profiling of Defa6-tdTomato+ cells isolated from mouse colon tumors.
2025-04-01 | E-MTAB-13752 | biostudies-arrayexpress
Project description:Barrier epithelia are essential to organismal homeostasis, and changes in their cellular composition are observed in human diseases. Within the small intestine, adult stem cells establish tissue cellularity, and may provide a means to control the abundance and quality of specialized epithelial cells. Nevertheless, we lack suitable approaches to identify biological targets and small molecules to modulate them. Here, we develop an extendable framework utilizing a physiologically-inspired organoid model to identify unknown, druggable regulators of intestinal stem cell differentiation that translate to intended manipulations in vivo. Specifically, we miniaturize and adapt an organoid model of Paneth cell differentiation to enable multiplexed phenotypic screening on the scale of thousands of samples, and employ longitudinal single-cell RNA-sequencing to understand hit biology. Strikingly, we identify that inhibitors of the nuclear exporter XPO1 modulate stem cell fate commitment, significantly increasing the abundance of Paneth cells independent of known differentiation cues. Our framework elucidates small molecules which modulate tissue stem cell biology and their underlying targets without the need for a priori knowledge of in vivo pathway biology.
2021-09-16 | GSE148524 | GEO
Project description:Aberrant CpG methylation is a universal trait of cancer cell genomes and can result in epigenetic modulation of gene activity; however, at which stages tumour-specific epigenetic patterns arise is unknown. Here, we analyse the methylome of APCM in mouse intestinal adenoma as a model of intestinal cancer initiation, and inventory a map of over 13,000 adenoma-specific recurrent differentially methylated regions (DMRs). We find that multiple genes coding for Polycomb proteins are upregulated in adenoma, and concomitantly, hypermethylated DMRs form preferentially at Polycomb target sites. We establish that DMRs are absent from proliferating intestinal epithelial cells or intestinal stem cells, and thus arise de novo after loss of APC. Importantly, a core set of DMRs is conserved in human colon cancer, defining a class of early epigenetic alterations that are distinct from known sets of epigenetically silenced tumour suppressors. The data presented suggests a sequence of events that leads to an altered methylome of colon cancer cells, and may allow more specific selection of clinical epigenetic biomarkers. Analysis of the methylome and RNA expression in adenoma of Apc-Min/+ mutant mice and of normal intestine in Apc-Min/+ and Apc-+/+ wild type mice.
2013-04-03 | E-GEOD-38983 | biostudies-arrayexpress
Project description:The development and severity of inflammatory bowel diseases (IBD) and other chronic inflammatory conditions can be influenced by host genetic and environmental factors, including signals derived from commensal bacteria. However, the mechanisms that integrate these diverse cues remain undefined. Here we demonstrate that intestinal epithelial cells (IECs) isolated from IBD patients exhibit decreased expression of the epigenome-modifying enzyme histone deacetylase 3 (HDAC3). Further, genome-wide analyses of murine IECs that lack HDAC3 (HDAC3ΔIEC) revealed that HDAC3 deficiency resulted in dysregulated gene expression coupled with alterations in histone acetylation. Critically, conventionally-housed HDAC3ΔIEC mice demonstrated loss of Paneth cells, impaired IEC function and alterations in the composition of intestinal commensal bacteria. In addition, HDAC3ΔIEC mice exhibited significantly increased susceptibility to intestinal damage and inflammation, indicating that epithelial expression of HDAC3 plays a central role in maintaining intestinal homeostasis. Strikingly, rederivation of HDAC3ΔIEC mice into germ-free conditions revealed that dysregulated IEC gene expression, Paneth cell homeostasis, and intestinal barrier function were largely restored in the absence of commensal bacteria. Collectively, these data indicate that the HDAC3 is a critical factor that integrates commensal bacteria-derived signals to calibrate epithelial cell responses required to establish normal host-commensal relationships and maintain intestinal homeostasis. In this study, we performed gene expression profiling to examine how the transcriptional profiles in primary live, EpCAM+ IECs from the large intestine differed between germ-free control HDAC3FF mice (3 biological replicates) and germ-free IEC-intrinsic knockout HDAC3ΔIEC mice (3 biological replicates).
2013-11-12 | E-GEOD-50189 | biostudies-arrayexpress
Project description:The development and severity of inflammatory bowel diseases (IBD) and other chronic inflammatory conditions can be influenced by host genetic and environmental factors, including signals derived from commensal bacteria. However, the mechanisms that integrate these diverse cues remain undefined. Here we demonstrate that intestinal epithelial cells (IECs) isolated from IBD patients exhibit decreased expression of the epigenome-modifying enzyme histone deacetylase 3 (HDAC3). Further, genome-wide analyses of murine IECs that lack HDAC3 (HDAC3?IEC) revealed that HDAC3 deficiency resulted in dysregulated gene expression coupled with alterations in histone acetylation. Critically, conventionally-housed HDAC3?IEC mice demonstrated loss of Paneth cells, impaired IEC function and alterations in the composition of intestinal commensal bacteria. In addition, HDAC3?IEC mice exhibited significantly increased susceptibility to intestinal damage and inflammation, indicating that epithelial expression of HDAC3 plays a central role in maintaining intestinal homeostasis. Strikingly, rederivation of HDAC3?IEC mice into germ-free conditions revealed that dysregulated IEC gene expression, Paneth cell homeostasis, and intestinal barrier function were largely restored in the absence of commensal bacteria. Collectively, these data indicate that the HDAC3 is a critical factor that integrates commensal bacteria-derived signals to calibrate epithelial cell responses required to establish normal host-commensal relationships and maintain intestinal homeostasis. In this study, we performed gene expression profiling to examine how the transcriptional profiles in primary live, EpCAM+ IECs from the large intestine differed between control HDAC3FF mice (3 biological replicates) and IEC-intrinsic knockout HDAC3?IEC mice (3 biological replicates).
2013-11-12 | E-GEOD-50188 | biostudies-arrayexpress