All immature gut cells have same chance at stem cell status

Contrary to previous assumptions about stem cell development, all cells in the fetal gut have the potential to develop into stem cells, according to a new study.

The development of immature intestinal cells is not predetermined. Instead, the cells’ immediate surroundings in the intestines affect their development, the researchers report.

This discovery may ease the path to effective stem cell therapy, says Kim Jensen, an associate professor from the Biotech Research & Innovation Centre and the Novo Nordisk Foundation Center for Stem Cell Biology at the University of Copenhagen.

“In principle, it is simply a matter of being in the right place at the right time.”

“We used to believe that a cell’s potential for becoming a stem cell was predetermined, but our new results show that all immature cells have the same probability for becoming stem cells in the fully developed organ. In principle, it is simply a matter of being in the right place at the right time. Here signals from the cells’ surroundings determine their fate. If we are able to identify the signals that are necessary for the immature cell to develop into a stem cell, it will be easier for us to manipulate cells in the wanted direction.”

Stem cells maintain the organs in the body, and can also repair minor tissue damage. A better understanding of the factors that determine whether or not an immature cell develops into a stem cell may therefore be useful in the development of stem cells for therapy and transplantation.

Stem cell transplantation and therapy make it possible to supplement the body’s own cells with new, healthy stem cells that can help repair or replace damaged tissue.

“We have gained greater insight into the mechanisms through which cells in the immature intestines develop into stem cells. Hopefully we are able to use this knowledge to improve treatment of non-healing wounds, e.g. in the intestines,” says Jensen.

“So far, though, all we can say for sure is that cells in the gastrointestinal tract have these characteristics. However, we do believe this is a general phenomenon in fetal organ development.”

The researchers began their work searching for understanding of what controls the destiny of intestinal stem cells. Jordi Guiu, a postdoctoral researcher at the Biotech Research and Innovation Centre, developed a method for monitoring the development of the individual intestinal cells. By introducing luminescent proteins into the cells he could, using advanced microscopy, monitor the development of the individual cells.

After the initial tests, the cells that researchers previously believed to be fetal stem cells were only able to explain a fraction of the growth of the intestines during fetal development.

When the researchers studied the data more closely, they arrived at the surprising hypothesis that all intestinal cells may have the same chance of becoming stem cells. The researchers proved the hypothesis in subsequent tests.

“The next step is to determine precisely which signals are necessary for immature cells to develop into the kind of stem cells we need. This is one of our research focusses,” says Jensen.

The results appear in Nature.

Additional researchers at the University of Cambridge contributed to the work. The European Research Council, the Horizon 2020 research program, the Lundbeck Foundation, the Novo Nordisk Foundation, the Carlsberg Foundation, and the Marie Curie fellowship program funded the project.

Source: University of Copenhagen