A study published in “Nature” reveals an exciting new mechanism that could change our understanding of what a stem cell is. Their findings may have important implications for our understanding of what a stem cell really is and how to use it in medical applications.
The intestine is a wonderful place. A special layer of cells lining the inside of the small and large intestine absorbs ingested nutrients and water and keeps anything harmful out of your system. This layer is called the intestinal epithelium, and it completely renews itself every four to seven days using stem cells.
These, explain Bernat Corominas-Murtra, from the University of Graz, and Edouard Hannezo, from the Austrian Institute of Science and Technology (ISTA), are a special type of cell that can self-renew by dividing and differentiating to give rise to any other type. of cells to renew their organs. However, scientists still don’t know exactly how they make these decisions, or what defines a stem cell.
Corominas-Murtra and Hannezo worked together with an international group of researchers to study stem cells in the intestinal epithelium.
The intestinal epithelium is just a layer of thick, constantly renewing cells. The villi that look like little tentacles that cover the inside of the small and large intestines are everywhere. Between the villi, there are small pockets in the tissue called intestinal crypts.
“Deep in the crypts, epithelial stem cells are constantly dividing. Some of the resulting cells remain as stem cells in the crypt and others are pushed to the tips of the surrounding villi,” he explains. Corominas-Murtra. “There they differentiate into functional cell types that allow intestinal function and that are discarded after a few days.”
The intestinal epithelium is just a layer of thick cells and is constantly being renewed.
While studying these stem cells in the small and large intestines, the scientists were initially stumped. “What we usually think of stem cells is that being a stem cell is determined by the intrinsic biochemical properties of a cell, something like a biochemical marker that we can identify,” Corominas-Murtra continues.
But, he says, “we found that among the cells that had this traditional stem cell marker, many of them never really functioned as stem cells, but instead are flushed out of the crypts to be discarded, not contributing to long-term turnover at all.” of the intestine. 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 working as stem cells in the small intestine than in the large intestine.”
In other words, he continues, “we discovered that, depending on their location, these cells behave like a stem cell or not. Cells in the epithelium are not only pushed out of the crypt by cell divisions below them, like on a conveyor belt, but there is another kind of movement involved,” explains Corominas-Murtra.
Depending on their location, these cells behave like a stem cell or not.
Bernat Corominas-Murtra
University of Graz
The scientists discovered that cells in the epithelium layer are also actively moving in random directions, back and forth along the conveyor belt, so to speak. In this way, cells that have already been pushed along the conveyor belt for a moment can end up back at the base of the crypt and act there again as stem cells to divide and replenish the epithelium.
Hannezo highlights the possible implications of these findings: “These movements constitute a new environmental mechanism that determines which cells come to act functionally as stem cells.. In the small intestine, the molecular signal that regulates movements is stronger than in the large intestine, so cells can return more frequently to the crypt. This explains why there are more functioning stem cells in the small intestine than in the large intestine. This could have important implications for our understanding of what a stem cell really is and how to use it in medical applications.”
This perspective builds on previous research by Corominas-Murtra and Hannezo at ISTA and the work of the Van Rheenen group.
With a background in physics, Corominas-Murtra and Hannezo created a advanced mathematical model of the intestinal epithelial layer including movement of cells to and from the crypt. Using such a model, they were able to predict the number of actually functioning stem cells in the small and large intestines.
Other research groups across Europe designed experiments using the latest methods in microscopy and genetics to test the predictions and found them to be accurate. They even tried to inhibit the chemical signal in the crypts and found that this reduced the number of functioning stem cells as predicted.