Our intestinal tissue doesn’t need a New Year’s resolution to keep up its amazing productivity. Our intestinal epithelium is replenished at breakneck speed in an assembly line that begins with stem cells. Today’s image is from a recent Development paper that discusses the importance of Notch signaling in stem cell self-renewal and intestinal homeostasis.
Our intestinal epithelium is folded and shaped into finger-like villi (“shaggy hair” in Latin) that increase the surface area of the tissue for more nutrient absorption. Each villus has several populations of cells in homeostasis in order to maintain function and constant replenishment. This production of epithelium starts with the actively-dividing crypt base columnar (CBC) stem cells that sit in the crypts. Although the identity of these cells has been known for a while, the factors regulating CBC stem cell self-renewal and differentiation were not well understood. A recent Development paper discusses the role for Notch signaling in CBC stem cell function. According to VanDussen and colleagues, Notch signaling is required for CBC stem cell self-renewal and survival. Notch inhibition caused a decrease in the number CBC cells, as well as precocious differentiation of more specialized intestinal cell types. VanDussen and colleagues showed that Notch regulates CBC cell self-renewal and cell fate choice through different pathways and by targeting different cell populations. In the images above, intestinal tissue was stained for a marker of CBC stem cells (Lgr5, green) and for proliferating cells (Ki67, red). In normal tissue (left), CBC stem cells were found at the base of the crypts, some of which were also actively dividing (arrows). Notch inhibition (right) resulted in a misshapen morphology of CBC stem cells, a decrease in the CBC cell marker, and a drop in the number of CBC cells that were actively dividing (arrowheads on left).
VanDussen, K., Carulli, A., Keeley, T., Patel, S., Puthoff, B., Magness, S., Tran, I., Maillard, I., Siebel, C., Kolterud, A., Grosse, A., Gumucio, D., Ernst, S., Tsai, Y., Dempsey, P., & Samuelson, L. (2011). Notch signaling modulates proliferation and differentiation of intestinal crypt base columnar stem cells Development, 139 (3), 488-497 DOI: 10.1242/dev.070763