Your gut is a wondrous place. A special layer of cells that coats the insides of your small and large intestines takes in nutrients and water from what you ate while keeping anything bad out of your system. This layer is called the intestinal epithelium. It completely renews itself every four to seven days using stem cells. These are a special cell type that can both self-renew by dividing and differentiated to give rise to any other types of cells to renew your organs. Scientists still do not know how exactly they make these decisions however, or what defines a stem cell.

An international group of experimental researchers studies the stem cells in the intestinal epithelium. They found an exciting new mechanism that could change our understanding of what a stem cell is. Their findings have now been published in the journal Nature.

The intestinal epithelium is just one layer of cells thick and constantly renewed. It is all over the villi which look like tiny tentacles covering the insides of the small and large intestines. Between the villi, there are tiny pockets in the tissue called intestinal crypts. That name may invoke some mystery and that may be not too far off what really happens there.

“At the bottom of the crypts, stem cells in the epithelium are constantly dividing. Some of the resulting cells remain as stem cells in the crypt and the others are pushed outwards towards to tip of the surrounding villi,” the author explains, “there, in the end, they differentiate into functional cell types that allow intestinal function and which are discarded after a few days. This happens all the time inside your body and if this mechanism breaks down, you can get into serious medical trouble.”

While studying these stem cells in the small and large intestines, the scientists were initially perplexed. “How we usually think of stem cells is that being a stem cell is determined by intrinsic biochemical properties of a cell – something like a biochemical marker we can identify,” the author continues.

“We found that among the cells that had this traditional stem cell marker, many of them never actually worked as stem cells but were pushed out of the crypts to be discarded instead, without contributing at all to the long-term renewal of the gut. We also saw that while classical markers predicted about the same number of stem cells in both the small and large intestines, there were about twice as many of them actually working as stem cells in the small intestine than in the large intestine.”

The scientists therefore wanted to understand what determines which cells actually act as stem cells and they found a surprising new mechanism that regulates the stem cells in the crypts.

“We found that whether these cells behave as a stem cell or not is all about their location! Cells in the epithelium are not just pushed outwards from the crypt by the cell divisions below them – like on a conveyor belt – but there is another kind of motion involved,” the author explains.

The scientists found that cells in the epithelium layer also actively move around in random directions – back and forth along the conveyor belt if you will. This way, cells that were already pushed along the conveyor belt for a bit can end up back at the base of the crypt, and act there again as stem cells to divide and replenish the epithelium.

Another author explains the possible implications of these findings, “These movements constitute a new environmental mechanism that determines which cells get to functionally act as stem cells. In the small intestine, the molecular signal regulating the movements is stronger than in the large intestine, so cells can move more frequently back into the crypt. This explains why there are more actually working stem cells in the small intestine than in the large ones. This could have major implications for our understanding of what a stem cell actually is and how to use them in medical applications.”

https://www.nature.com/articles/s41586-022-04962-0