The epithelial lining of the small intestine needs to be refreshed by stem cells every few days to stay functional. For the first time, in a study by the Hubrecht Institute, the behavior of these stem cells has been caught on tape.
Dr Jacco van Rheenen of the Hubrecht Institute and his colleagues developed high resolution microscopy techniques to record videos of adult stem cells in the intact small intestine of living mice. These videos led to surprising new insights into the behavior of stem cells.
From prior studies we know that the small intestine exists of 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, stem cells compete constantly for space and eventually one stem cell wins the competition and replaces all other stem cells within the crypt and will be the 'mother' cell for all other more specialized cells in the crypt and adjacent villi.
In this study, Van Rheenen and colleagues questioned 'Are all stem cells equally competitive, or is there a superior subpopulation?' After catching the stem cells on tape, they analyzed the competitive behavior of every stem cell within the stem cell niche. This revealed that all 14 to 16 stem cells within each crypt have the ability to win the competition and therefore are able to refresh the epithelial layer of the adjacent villus. Surprisingly, stem cells at the center of the niche have 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.'
The work of Dr van Rheenen and colleagues has be published on 16 February 2014 in the advanced online publication of Nature. Biophysicist Dr van Rheenen is group leader at the Hubrecht Institute. He and his team are specialized in visualizing the behavior of individual healthy and tumor cells in living mice. The new insights into stem cell behavior are important to understand how tissue is refreshed, and how DNA damage can accumulate in stem cells driving uncontrolled growth leading to cancer.
The Hubrecht Institute is a research institute of the Royal Netherlands Academy of Arts and Sciences and is affiliated with the University Medical Center Utrecht.
Ritsma L, Ellenbroek SIJ, Zomer A, Snippert HJ, de Sauvage FJ, Simons BD, Clevers H, van Rheenen J. (2014) Intestinal crypt homeostasis revealed at single-stem-cell level by in vivo live imaging. Nature, AOP 16 February 2014.