Chromatin silencing maintains the identity of intestinal stem cells
The epithelial sheet of the small intestine harbors villi structures in the lumen and invaginations to form the crypts of Lieberkühn (1). Intestinal stem cells (ISCs) at the bottom of the crypts give rise to Paneth cells and transit-amplifying cells that are capable of differentiating into different types of cells that are components of the small intestine (1). Hierarchies of stem cell models suggest that there are 4 to 6 stem cells per crypt, which decide the ultimate pattern of the entire crypt (2). Two models were originally established for ISCs: the +4 label retaining cell (LRC) model and the crypt base columnar cell (CBC) or Lgr5+ cell model (2,3). Wnt signaling is known to be essential for Lgr5+ ISCs, and the bottom of the crypt is thought to be a stem cell niche in which Wnt signaling crosstalks with other signaling pathways in regulating self-renewal of ISCs as well as their differentiation, proliferation and migration (4).