Intestinal epithelial stem cells in the adult

Question 1

What is the purpose of the epithelial in intestine?

Answer 1

This layer of cells is a monolayer and has a very important role in shielding the intestine from the outer environment. Represents the exterior of the body and that means that there is a risk that anything that gets into the GIT will also get into the body.
Populated by lots of micro-organisms known as the gut microbiota. They have established a commensal relationship with us over time and this enables us to make use of some nutrients which would otherwise be indigestible. Also potential pathogens will be held in check by competition of commensal bacteria.

Question 2

Stem cells are present where in the intestinal epithelial?

Answer 2

The abse of the crypts, they move up the vili as they differentiate.

There is high turnover of the cells in the intestine due its acidic/enzymatic nature.

Question 3

What can be said of the cells of the crpyt?

Answer 3

~250 of them,
10-15 are stem cells witch a distinctive morphology.

Intestinal SC are not quiescent at all: they are actively cycling up the vili to replace lost cells. (whole lining replaced every 5-6 days)

They all expres LGR5+, a target of the WNT signalling pathway.

Question 4

Wnt signalling is ________ in colorectal cancer.

Answer 4

increased.

Question 5

80% of colorectal cancers harbour inactivating mutations in ______ a tumour suppressor that forms part of the beta-catenin destruction complex

Answer 5

APC

Question 6

What types of cells within the crypts produce membrane bound WNTs and what is the significance of the membrane localisation?

Answer 6

Paneth cells.

Shows that they are only working to stimulate WNT signalling on the surrounding cells.

Question 7

How does the localisation of WNTs to paneth cells in the crypt maintain the niche?

Answer 7

• R-spondins associating with ligand – increases the strength of the signal. Tethered to the membrane. Led to the development for ‘spacial contraint’ model of how the SC compartment is maintained. The closer they get to the boundary the further away they are moving from the effects of the Wnts. They are no longer engaged with paneth cells or wnts and will no longer be stem cells. This maintains the niche at the base of the crypt. A single stem cell division will remain in lineage as a stem cell (the other cell can be too far away and this will trigger differentiation) - asymmetric