Postnatal epigenetic development of mouse intestinal stem cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE58532 | GEO | 2015/08/25
SECONDARY ACCESSION(S): PRJNA252849
REPOSITORIES: GEO
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Project description:We used unbiased whole genome bisulfite sequencing (WGBS) to identify DNA methylation changes in the intestinal stem cells (ISCs) or their progeny during the suckling period of mouse colon development. Lgr5-EGFP mice were used to identify ISC populations in the colons. WGBS were performed using EGFP labeled Lgr5+ ISCs and epithelial cell adhesion molecule (EpCAM) labeled epithelial cells isolated at the beginning and end of the suckling period (postnatal day 0-P0 and P21).
2015-08-25 | E-GEOD-58532 | biostudies-arrayexpress
Project description:We used RNA sequencing to quantify the gene expression levels in the intestinal stem cells (ISCs) or their progeny during the suckling period of mouse colon development. Lgr5-EGFP mice were used to identify ISC populations in the colons. RNA sequencing was performed using EGFP labeled Lgr5+ ISCs and epithelial cell adhesion molecule (EpCAM) labeled epithelial cells isolated at the beginning and end of the suckling period (postnatal day 0-P0 and P21).
2015-08-25 | E-GEOD-64054 | biostudies-arrayexpress
Project description:We used RNA sequencing to quantify the gene expression levels in the intestinal stem cells (ISCs) or their progeny during the suckling period of mouse colon development.
2015-08-25 | GSE64054 | GEO
Project description:Comparison of distal small intestine in IntraUterine Growth Restricted piglets fed either adequate or high protein artificial milks during suckling period. Comparison at 7 and 28 days of life. Keywords: Nutritional response
2010-01-01 | GSE18249 | GEO
Project description:Comparison of distal small intestine in IntraUterine Growth Restricted piglets fed either adequate or high protein artificial milks during suckling period. Comparison at 7 and 28 days of life. Keywords: Nutritional response 22 samples - One sample versus a pool
2010-05-16 | E-GEOD-18249 | biostudies-arrayexpress
Project description:Gene expression was analysed in the colon and brain of normal rat pups from late prenatal through early postnatal development. Tissue was isolated from pups one day prior to the anticipated date of birth and throughout the suckling period until the end of weaning.
2009-12-18 | GSE18133 | GEO
Project description:Intestinal epithelial stem cells (ISCs) are the focus of recent intense study. Current in vitro models rely on supplementation with the Wnt agonist R-spondin1 to support robust growth, ISC self-renewal, and differentiation. Intestinal subepithelial myofibroblasts (ISEMFs) are important supportive cells within the ISC niche. We hypothesized that co-culture with ISEMF enhances the growth of ISCs in vitro and allows for their successful in vivo implantation and engraftment. ISC-containing small intestinal crypts, FACS-sorted single ISCs, and ISEMFs were procured from C57BL/6 mice. Crypts and single ISCs were grown in vitro into enteroids, in the presence or absence of ISEMFs. ISEMFs enhanced the growth of intestinal epithelium in vitro in a proximity-dependent fashion, with co-cultures giving rise to larger enteroids than monocultures. Co-culture of ISCs with supportive ISEMFs relinquished the requirement of exogenous R-spondin1 to sustain long-term growth and differentiation of ISCs. Mono- and co-cultures were implanted subcutaneously in syngeneic mice. Co-culture with ISEMFs proved necessary for successful in vivo engraftment and proliferation of enteroids; implants without ISEMFs did not survive. ISEMF whole transcriptome sequencing and qPCR demonstrated high expression of specific R-spondins, well-described Wnt agonists that supports ISC growth. Specific non-supportive ISEMF populations had reduced expression of R-spondins. The addition of ISEMFs in intestinal epithelial culture therefore recapitulates a critical element of the intestinal stem cell niche and allows for its experimental interrogation and biodesign-driven manipulation. Two samples of intestinal subepithelial myofibroblasts were used in this study.
2013-12-20 | E-GEOD-52402 | biostudies-arrayexpress
Project description:Oncogenic mutations that drive colorectal cancer can be present in healthy intestines for long periods without overt consequence. Mutation of Adenomatous polyposis coli (Apc), the most common initiating event in conventional adenomas, activates Wnt signaling, hence conferring fitness on mutant intestinal stem cells (ISCs). Apc mutations may occur in ISCs that arose by routine self-renewal or by dedifferentiation of their progeny. Although ISCs of these different origins are fundamentally similar, it is unclear if both generate tumours equally well in uninjured intestines. Also unknown is whether cis-regulatory elements are substantively modulated upon Wnt hyperactivation or as a feature of subsequent tumours. Here, we show in two mouse models that adenomas are not an obligatory outcome of Apc deletion in either ISC source but require proximity of mutant intestinal crypts. Reduced crypt density abrogates, and aggregation of mutant colonic crypts augments, adenoma formation. Moreover, adenoma-resident ISCs open chromatin at thousands of enhancers that are inaccessible in Apc-null ISCs not associated with adenomas. These cis-elements explain adenoma-selective gene activity and persist, with little further expansion of the repertoire, as other oncogenic mutations accumulate. Thus, cooperativity between neighbouring mutant crypts and new accessibility at specific enhancers are key steps early in intestinal tumourigenesis.
2024-11-15 | GSE241380 | GEO
Project description:Oncogenic mutations that drive colorectal cancer can be present in healthy intestines for long periods without overt consequence. Mutation of Adenomatous polyposis coli (Apc), the most common initiating event in conventional adenomas, activates Wnt signaling, hence conferring fitness on mutant intestinal stem cells (ISCs). Apc mutations may occur in ISCs that arose by routine self-renewal or by dedifferentiation of their progeny. Although ISCs of these different origins are fundamentally similar, it is unclear if both generate tumours equally well in uninjured intestines. Also unknown is whether cis-regulatory elements are substantively modulated upon Wnt hyperactivation or as a feature of subsequent tumours. Here, we show in two mouse models that adenomas are not an obligatory outcome of Apc deletion in either ISC source but require proximity of mutant intestinal crypts. Reduced crypt density abrogates, and aggregation of mutant colonic crypts augments, adenoma formation. Moreover, adenoma-resident ISCs open chromatin at thousands of enhancers that are inaccessible in Apc-null ISCs not associated with adenomas. These cis-elements explain adenoma-selective gene activity and persist, with little further expansion of the repertoire, as other oncogenic mutations accumulate. Thus, cooperativity between neighbouring mutant crypts and new accessibility at specific enhancers are key steps early in intestinal tumourigenesis.
2024-11-10 | GSE281056 | GEO
Project description:For more than a century, fasting regimens have been shown to improve health, lifespan, and tissue regeneration in diverse model organisms and humans. However, important questions remain regarding how fasting and refeeding cycles stimulate stem cell output and how this influences their role in early tumor formation. Here, we demonstrate that in the mammalian intestine, a short 24-hour fast followed by a 24-hour refeeding period (that is, post-fast refeeding) and not fasting itself elevates the stemness program and regenerative capacity of Lgr5+ intestinal stem cells (ISCs). Furthermore, loss of the tumor suppressor APC in post-fast refed ISCs significantly boosts tumor incidence in the small intestine and colon compared to those in the fasted or ad libitum fed states. Mechanistically, robust induction of insulin-PI3K-mTORC1 signaling as well as elevated intestinal polyamines level increase protein synthesis in post-fast refed ISCs to mediate these changes as inhibition of mTORC1, polyamine, or protein synthesis abrogate the regenerative or tumorigenic effects of post-fast refeeding. Thus, our data indicate that post-fast refeeding leads to a burst not only in stem cell-driven regeneration but also in tumorigenicity and that careful consideration be given to fast-refeeding cycles when planning diet-based strategies.
2023-08-08 | GSE192482 | GEO