Researchers at the University of Colorado Cancer Center (USA) have solved the mystery of how ordinary intestinal cells transform into regenerative stem cells. This promising discovery could pave the way for new therapies for colorectal and other types of cancer.
Stem cells are undifferentiated cells capable of generating specialized cells in the tissues in which they are found. Typically, cells follow a classic cycle: they grow, divide, and then die.
Cell differentiation is an essential process in the development of multicellular organisms: it produces cells with unique functions, such as muscle cells, nerve cells, and red blood cells. This process is also central to the regeneration of tissues, particularly those that are constantly renewed, such as skin or blood. Once differentiated, a cell generally cannot return to its original state—with a few exceptions.
Professors Peter Dempsey, a pediatrician and biologist at the University of Colorado School of Medicine, and Justin Brumbaugh, an assistant professor of molecular, cellular, and developmental biology at the University of Colorado Boulder, published their findings in the journal Nature Cell Biology. The website EurekAlert relayed the highlights.
The intestine, champion of self-repair
Dempsey explains:
"The intestine has a remarkable ability to regenerate after injury. Intestinal cells can temporarily revert to a regenerative stem cell state to repair damage, before returning to their normal role."
Finding the key to the process
According to Brumbaugh, scientists have long been searching for the molecular "trigger" that enables this reversal. Using animal models, the team identified a biochemical modification of the histone H3 protein as responsible for turning this flexible cellular state on or off. Histones play a fundamental role in regulating gene expression.
Brumbaugh clarifies:
"Intestinal cells must maintain their identity to function properly. If they change when they are not needed, they lose their specialization, a phenomenon closely linked to the development of cancer."
Towards new therapeutic strategies
Researchers now want to target this mechanism to block or activate it at will, in order to treat diseases such as colorectal cancer or other chronic inflammatory bowel diseases that can develop into cancer.
Dempsey adds:
« This mechanism appears to be involved in cell differentiation." If it is blocked, cells can revert to a regenerative stem cell state. »
He also points out that certain forms of colorectal cancer have exactly this genetic profile of regeneration, which is also found in pathologies such as chronic colitis or inflammatory bowel diseases.
A link with treatment resistance
This mechanism could also explain increased resistance to chemotherapy or radiotherapy:
"When a cell reverts to a regenerative stem cell state, it often becomes more resistant to treatments, which is a real challenge."
And he concludes:
« In some non-cancer patients undergoing aggressive treatments, one of the side effects is the destruction of the stem cell layer of the intestine. If the dose is poorly calibrated, this can lead to a complete loss of the intestinal wall. By better understanding this mechanism, we could better protect these cells. »
This discovery marks a major advance in the understanding of intestinal cell function and opens up new therapeutic perspectives.
