Stem cell competition caught on tape

The epithelial lining of the small intestine needs to be regenerated by stem cells every few days in order to stay functional. Researchers from the Hubrecht Institute have captured recordings of these stem cells in living mice. The recordings and their accompanying study can be found in the online journal Nature.

From prior studies it was known the small intestine contains large numbers of villi (finger-like protrusions that provide the absorptive area for food) and crypts (invaginations that include 14 to 16 adult stem cells). Since stem cells multiply rapidly, they compete constantly for space. Eventually one stem cell ‘wins’ the competition and replaces all other stem cells within the crypt. This will be the ‘mother’ cell for all other more specialised cells in the crypt and adjacent villi.

Biophysicist Dr Jacco van Rheenen and his colleagues wondered if all stem cells are equally competitive, or if there is a superior subpopulation. They developed high-resolution microscopy techniques to record video of the stem cells, which led to surprising new insights into their competitive behaviour.

All 14 to 16 stem cells within each crypt had the ability to win the competition and therefore are able to refresh the epithelial layer of the adjacent villus. Surprisingly, stem cells at the centre of the crypt had a positional advantage and therefore a higher chance to replace all other stem cells than stem cells at the border.

“However, our videos also showed that stem cells are moving within the crypt and therefore the positional advantage of central cells can be lost,” said Dr van Rheenen.

Van Rheenen specialises in visualising individual cells in living animals. The latest insights into stem cell behaviour are important to understanding how tissue is refreshed and how DNA damage can accumulate in stem cells, driving uncontrolled growth leading to cancer.