The functioning of stem cells is revealed a little more

Stem cells have the ability to develop into different cell types, including repairing damaged tissue. However, sometimes they lose this ability, without anyone understanding why. A new study, published in the journal Nature, also seeks to understand the future development of these cells. Researchers from the Novo Nordisk Foundation Stem Cell Biology Center (DanStem) at the University of Copenhagen (Denmark) have discovered how stem cells lose their potential to multiply and “forget their past”. During their work, the researchers discovered that proteins called transcription factors may have a different role than they had previously thought.

The study of signals

For the past 30 years, the accepted belief was that transcription factors stimulate gene expression by turning them on or off, thereby triggering changes. The scientists also believed that transcription factors were behind the process of determining whether a gene was expressed and translated into the corresponding protein. This new study shows that the function of transcription factors may be more comparable to that of the cell’s memory.

As long as transcription factors are linked to a gene, it can be activated. According to Josh Brickman, professor and group leader at DanStem, external factors determine whether the gene is activated or not. Cells cannot return to the point of origin in the absence of transcription factors. The question of how slowly a cell develops from state to state is central to understanding the behavior of multicellular organisms. Stem cell researchers consider this vital, which is why they are constantly trying to refine techniques to transform the most basic cells of the human body into various specific types of cells that can be used for different purposes, such as the regeneration of damaged tissues. Until now, it has been extremely difficult to study the signals necessary for cells to change their identity.

Mimicking a cell’s response to signaling, the researchers developed a stem cell model to examine the events that led to the gene turning on or off in response to signals received. They also studied the circumstances in which cells grow in a particular direction, but chose to reverse that direction. This work also involved the use of advanced mass spectrometry to measure how cellular proteins are modified by phosphorylation, that is, the addition of a phosphate group. This was done in collaboration with Jesper Olsen’s group at the Novo Nordisk Foundation Protein Research Center. This agreement has facilitated a better understanding of how individual proteins in a cell react to external signals, explains Josh Brickman.

Surprising results

Although the sequence of cellular transcription processes could not be measured as precisely as this study, the commonly accepted position was that transcription factors turned the gene on or off to initiate its transcription. This is not the case with embryonic stem cells and other varieties of cells.

Although transcription factors are an important signal, they do not drive the process. “Once they’re there, the gene can be read, and they stay put for a while after it’s read. When they’re gone, the window in which the gene can be read closes,” says William Hamilton, first author of the study and assistant professor at DanStem. To illustrate this point, the researcher takes the example of the vapor trails left in the sky by planes after they have passed. “They linger for a while and slowly dissipate again.”

This discovery changes our perception of molecular biology and is particularly important for researchers working in the field of stem cells and cancer biology. The study gives us new insights into cell development, the pathways involved in determining how they change and when they can’t. As these pathways are often found to be mutated in cancer patients, this study will allow researchers to study cancer.