Quantifying the spatio-temporal cell dynamics in the intestinal epithelium under homeostasis
Quantifying the spatio-temporal cell dynamics in the intestinal epithelium under homeostasis and in altered conditions
The epithelium lining the intestine comprises invaginations or crypts, and, in the case of the small intestine, evaginations towards the lumen or villi. The epithelium is subjected to a constant renewal process driven by stem cells located at the base of the crypts where they proliferate and differentiate while migrating along the crypt-villus axis in the small intestine or onto the flat surface of the large intestine, before being shed into the gut lumen. The intestinal epithelium forms a barrier between the body and the gut content continuously exposed to internal and foreign stimuli. The mechanisms to maintain and recover the equilibrium between cell proliferation, migration and shedding and the response of the stem cells following perturbations are not yet understood.
We have developed computational and analytical models that integrated with imaging and lineage tracing experimental strategies enable the quantification of the spatio-temporal cell dynamics along the crypt-villus axis as well as proliferation, differentiation and clonal expansion of the stem cell population. This approach is being applied to answer specific questions on the regulation of the intestinal epithelium and on the response of stem cells under homeostasis and in altered conditions.
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