Intestinal Stem Cell Differentiation

#1

Paneth cells are in the niche with stem cells

#2

Wnt signaling allows paneth cells to express delta and stem cells to express notch (occurs in the crypt)

• The role of delta and notch at the base of the crypts is to prevent stem cells from differentiating. Too much Wnt means there will not be enough differentiation leading to the overproliferation of stem cells. Under normal conditions, Wnt signaling allows paneth cells to express delta. Paneth cells are then activating notch to prevent differentiation.

#3

The stem cells divide into two different cells through stoichastic control. Here both differentiate.

• Self renewal occurs in later divisions to produce necessary stem cells

• Paneth cells prevent differentiation of stem cells

#4

The result is two stem-like cells that have changed position; they are no longer at the base in contact with paneth cells. They are in a new environment where they will undergo lateral inhibition to decide which cell will differentiate in which way.

• During lateral inhibition, we look/wait for a drop in delta, through transient bias, in one of the cells, creating an asymmetry that allows the cell with slightly more delta to bind notch and completely turn off delta in the cell that showed the initial drop in delta protein.

#5

The cells that “win” lateral inhibition will become secretory cells (ex. Mucus goblet cells)

#6

The cells that lose and have notch activated, undergo further division and then differentiate into common absorptive cells.