Li lab

Stem Cell and Cancer Biology Laboratory

: Wnt signal regulation in intestinal stem cell homeostasis

In the adult intestine, stem cells reside at the crypt bottom to maintain self-renewal of the epithelium. Early progenitors in the intestinal crypt are highly dynamic for lineage selection, yet permit plasticity for reacquiring multipotency upon damage. Intestinal stem cell homeostasis is controlled by a number of signalling pathways, including the two key developmental pathways - Wnt and Notch.

Intestinal stem cells proliferate and give rise to daughter cells, which will then commit to specific lineages for terminal differentiation when migrating up the villus. Upon stem cell damage, the committed progenitors have the capacity to dedifferentiate and reacquire a stem cell state for regeneration. Previous studies have shown that Wnt signalling is required for stem cell maintenance, while Notch is crucial for lineage specification.

Wnt signalling activates many downstream target gene transcriptions, yet Wnt target genes come in two flavours: 'crypt-gradient' and 'stem-cell restricted'. We are interested to study how the expression of stem cell-specific Wnt targets is regulated. We investigate the molecular mechanism that controls the expression pattern of these stem cell-expressing Wnt target genes, which might shed light on the mechanism that defines intestinal stem cell spatial positioning.