Project description:We report the application of bulk RNAseq assay in examining the dietary effect on mouse intestinal stem cell (ISC) subpopulation. Lgr5EGFPcreERT2 mice were fed with new western diet 1 (NWD1) or the control AIN76A diet for 3 or 12 months, to investigate differential dietary effect. To examine the reversibility of dietary effect, after 3 months of NWD1 feeding, the mice were switched to AIN feeding, and examined at 6 or 12 months old.

2023-04-12 | GSE186811 | GEO

Region-specific proteome changes of the intestinal epithelium during aging and dietary restriction

Project description:The small intestine is responsible for nutrient absorption and it is one of the most important interfaces between the environment and our body. During aging, changes in the structure of the epithelium lead to food malabsorption and reduced barrier function thus increasing disease risk in aging. The molecular drivers of these alterations remain poorly understood. Here, we compared the proteomes of small intestinal crypts from mice across different anatomical regions and age groups. We found that aging alters epithelial immune responses, metabolic networks and stem cell proliferation, and it is accompanied by a region-dependent skewing in the cellular composition of the intestinal epithelium. Of note, a short period of dietary restriction followed by re-feeding partially restores the epithelium to a youthful state by promoting the differentiation of intestinal stem cells (ISCs) towards the secretory lineage. Using in vitro and in vivo studies, we identify Hmgcs2 (3-hydroxy-3-methylglutaryl-CoA synthetase 2) – the rate limiting enzyme in the synthesis of ketone bodies – as a modulator of ISCs differentiation, which responds to dietary changes. This study provides an atlas of age-dependent proteome changes in defined regions of the intestinal epithelium and characterizes how young and old mice adapt to drastic changes of diet, such as dietary restriction and re-feeding.

2020-04-29 | PXD014311 | Pride

Stem cell intrinsic nutrient sensing regulating diet dependent intestinal adaptation

Project description:The intestine is an organ with exceptionally high rate of cell turnover and perturbations in this process can lead to disease such as cancer or intestinal atrophy. Nutrition is a key factor regulating the intestinal cell turnover and has a profound impact on intestinal volume and cellular architecture. However, how the intestinal equilibrium is maintained in fluctuating dietary conditions is insufficiently understood. By utilizing the Drosophila midgut as a model, we reveal a novel nutrient sensing mechanism coupling stem cell metabolism with stem cell extrinsic growth signal. Our results show that intestinal stem cells (ISCs) employ the hexosamine biosynthesis pathway (HBP) to monitor nutritional status and energy metabolism. Elevated activity of the HBP promotes Warburg effect-like metabolic reprogramming, which is required for the reactivation of ISCs from calorie restriction-induced quiescence. Furthermore, the HBP activity is an essential facilitator for insulin signaling-induced intestinal growth. In conclusion, intestinal stem cell intrinsic nutrient sensing regulates metabolic pathway activities, and defines the stem cell responsiveness to niche-derived growth signals.

2018-09-13 | GSE107052 | GEO

The effect of dietary fibre exposure on gene expression profiles in intestinal Caco-2 cells

Project description:Background: Human intestinal tissue samples are barely accessible to study potential health benefits of nutritional compounds. Dietary fibres have been descirbed to be beneficial for intestinal health. Therefore, in this study we explored the applicability of an in vitro model, namely human intestinal Caco-2 cells, to study the effect of dietary fibres on intestinal health. Transcriptomics was applied to obtain more insight into their mode of actions in the intestinal cells. Methods: Caco-2 cells were stimulated with 500 ug/ml dietary fibres and the maximal observed LPS contamination to serve as background control for 6 hours, total RNA was extracted and Affymterix Human Gene 1.1 ST arrays were used to analyze the gene expression profiles. To identify dietary fibre induced gene expression profiles in dietary fibre gene responses were compared to medium samples. Furthermore, to analyse differentiatlly affected pathways Ingenuite Pathway Analysis was employed. Results: Pathway analysis revealed a distinct separation between the dietary fibres. GOS and beta-glucan oat medium viscosity affected transcription of a lower amount of genes (gene cut-off p<0.05) and gen transcription changes suggest an increase in vesicle transport and altered cholesterol regulation. On the other hand, the other dietary fibres differentially regulated a larger numbers of genes (gene cut-off p<0.05) and all appeared related to immune responses. We observed an increase in intracellular and extracellular anti-bacterial pathways and production of cytokines specifically aimed at communication with the adaptive immune system. Conclusion: GOS and beta-glucan oat medium viscosity appeared to induce intestinal epithelial communication with the body, whereas the other dietary fibres appeared recognized as PAMP and induce epithelial cells to interact with the immune system.

2022-05-30 | GSE99610 | GEO

High fat effect on mouse intestinal stem cells

Project description:High fat effect on mouse intestinal stem cells

| PRJNA636084 | ENA