Intestinal stem cells

The intestinal epithelium is the primary barrier between the gut lumen and the underlying tissues and consists of a single cell layer. The epithelial cells arise from Lgr5+ intestinal stem cells (ISCs). These cells are located at the bottom of the crypt and upon cell division migrate upwards away from the stem cell niche and undergo differentiation.

Epithelial barrier breach may be a result of poor functioning of tight junction proteins or deficiencies in Goblet and Paneth cells, leading to an influx of bacteria into the crypts. Microbiota plays an important role in the onset of IBD, but currently it is unknown what a possible influx of bacteria towards the stem cell niche might mean in the context of disease onset or prolongation. Using the intestinal organoid model established by Sato and colleagues at the Clevers’ laboratory, we will expose organoids from IBD patients and healthy controls to microbiota to investigate the effect on normal homeostasis, and may identify harmful and beneficial bacteria in regard to normal functioning of the stem cells.