Intestinal epithelium is capable of rapid regeneration, which is associated with transient changes in cellular identity. Some of these changes involve an enrichment of fetal-like gene expression and simultaneous suppression of adult stem cell signature. Interestingly, the upregulation of fetal-like marker Stem cell antigen 1 (Sca1) is modulated by extracellular matrix (ECM) which is known to guide epithelial cells during regeneration. Our recently published decellularized small intestinal ECM (iECM) system retains the composition and topology of natural ECM. This makes it an attractive system for ex vivo studies addressing regeneration.
This thesis aimed to gain insight into the fetal-like identity and its dynamics using an ex vivo iECM system. Intriguingly, Sca1 expressing cells on iECM displayed migratory features, such as a leading edge and changes in nuclear morphology. Curiously, these features are typical for epithelial cells during development. Furthermore, based on marker gene expression during iECM re-epithelization, fetal-like state was upregulated while adult stem cell state was downregulated, revealing a gradually emerging inverse correlation. Additionally, data suggests that circadian rhythms may have a role in modulating the fetal-like state. iECM from an active-state mice indicated a reduced capability to induce fetal-like identity and overall re-epithelization compared to the rest-state iECM. The results of this thesis suggest further potential of iECM system in studying emergence of fetal-like state during re-epithelization and circadian rhythm impact on it.
