SIRT1 Inhibitors Mitigate Radiation-Induced GI Syndrome by Enhancing Intestinal Stem Cell Survival
In this study, the authors demonstrated that SIRT1 inhibitors were able to mitigate some of the effects of acute radiation exposure. SIRT1 inhibitors prevented GI syndrome and protected the ISC from being depleted following abdominal irradiation.
The serotonin reuptake transporter is reduced in the epithelium of active Crohn’s disease and ulcerative colitis
Our team recently came across an IBD study which demonstrated for the first time that the serotonin reuptake transporter protein is downregulated in inflamed intestinal tissue.
Human ileal organoid model recapitulates clinical incidence of diarrhoea associated with small molecule drugs
In this study the authors described the characterisation of a human 3D enteroid culture model for assessing drug-induced gastro-intestinal toxicity.
ACE2 contributes to the maintenance of mouse epithelial barrier function
A recent COVID-19 study has utilised organoids to look into the effects of deleting ACE2, the protein which the virus uses to enter the cell.
Lgr5+ telocytes are a signalling source at the intestinal villus tip
A recent study utilising spatially-resolved transcriptomics and laser capture microdissection has discovered that Lgr5+ telocytes act as a signalling source in the villus tip of the intestine.
CD47 is a negative regulator of intestinal epithelial cell self-renewal following DSS-induced experimental colitis
Scientists have demonstrated that epithelial cell CD47 expression in the colon is strongly induced in patients with ulcerative colitis and Crohn's disease.
Location-specific cell identity rather than exposure to GI microbiota defines many innate immune signalling cascades in the gut epithelium
A recent study established a biobank of human and murine GI organoids from tissue-resident stem cells and analysed gene expression to discover that the epithelial innate immune barrier follows a specific pattern per GI segment.
Regulatory network analysis of Paneth cell and goblet cell enriched gut organoids using transcriptomics approaches
A recent study used cell-enriched organoids in order to predict the key molecular regulators involved in Paneth cell and goblet cell specific functions.
The use of organoids to study the epithelial response to secreted pro-inflammatory cytokines
A recent organoid study suggests that Nfkb2 signalling pathway may be targetable to improve intestinal inflammation.
Genome-wide epigenetic and transcriptomic characterisation of human-induced pluripotent stem cell-derived intestinal epithelial organoids
Recent developments have allowed us to generate epithelial cell-specific intestinal organoids from pluripotent stem cells, we review a study which aims to characterise these organoid cultures and compare them with cultures derived from primary intestinal epithelial cells.
5-Fluorouracil treatment induces characteristic T>G mutations in human cancer
Organoid models treated with 5-FU suggest further oncology scrutiny is needed when treating younger patients
Derivation of adult canine intestinal organoids for translational research in gastroenterology
This study describes the development and long-term maintenance of small intestine and colon in vitro canine organoids using whole tissue and biopsy samples from 40 healthy and diseased cohorts.
Human 3D Gastrointestinal Microtissue Barrier Function As a Predictor of Drug-Induced Diarrhoea
New preclinical approaches are required for earlier testing of therapies for GI-toxicity. In this study the authors describe an in vitro human 3D GI microtissue and validated it for GI-toxicity using a panel of known drugs that do/do not cause diarrhoea.
Can organoids guide clinical decisions? Current successes and potential pitfalls
A paper in the Nature Medicine journal reviews the use of organoids in the clinic up-to-date and also highlights some of the potential obstacles for widespread use as predictive tools for in vivo treatment. Our Senior Scientist, Dr Sarah Hoyle, summarises the key points from this paper.
Human organoids provide new insights into early stage enterovirus infection
Epistem have presented developmental work within the organoid model in the areas of epithelial regeneration and GI toxicity at various conferences. Potential readouts in this model could be proliferation, differentiation, apoptosis, cytotoxicity screening and protein and gene expression.
Organoids programmed to differentiate into rare hormone-producing enteroendocrine cells
New paper describes protocols for the manipulation of organoid Lgr5+ stem cells into quiescence before being programmed to differentiate into specific intestinal lineages, including the rare hormone-producing endocrine cell