Retrograde movements determine effective stem cell numbers in the intestine

Azkanaz M, Corominas-Murtra B, Ellenbroek S et al. Retrograde movements determine effective stem cell numbers in the intestine. Nature 2022; 607: 548–554. doi: 10.1038/s41586-022-04962-0

The intestinal crypt is maintained by a population of stem cells that compete for space within the crypt base niche. Typically identified by Lgr5 (Leucine-rich repeat-containing G-protein-coupled receptor 5) expression, only a portion is capable of repopulating the crypt (effective stem cells). Azkanaz et al used intravital microscopy to permit real-time visualisation of labelled Lgr5+ stem cell dynamics within a live intestine. This technique revealed that while the small intestine (SI) and large intestine (LI) contained approximately the same number of Lgr5+ stem cells, there were two times as many effective stem cells in the SI as the LI. Defining the starting position within the crypt and following them over 8 weeks, stem cells on the niche border were often capable of remaining as effective stem cells in the SI, whereas none of the border Lgr5+ stem cells in the LI were capable of long-term repopulation. Imaging revealed that SI border Lgr5+ stems were able to move in a retrograde fashion down the crypt axis that LI border stem cells could not. SI crypts contain Paneth cells capable of producing Wnt (Wingless/Integrated) and 3D (three-dimensional) organoid tracing of Lgr5+ stem cells exposed to Wnt3a (Wnt family member 3a) demonstrated a clear increase in stem cell movement that could be prevented by a Wnt3a inhibitor. More effective stem cells increased the time for clonal conversion, indicating a higher rate of stem cell competition within the SI crypt. Therefore, stem cell capability is increased by retrograde movement and may explain differential tumour rates between SI and LI as tumours are derived from a single mutant crypt stem cell.

Exercise reduces weight through more than just burning calories

Li V, He Y, Contrepois K et al. An …