In 2006 japanese researcher Shinya Yamanaka discovered that it was possible to turn back the clock of the cells and get them back to a state similar to embryonic. Since then, cell reprogramming has been a revolution for science, although much remains unknown about the process.
A team from the National Cancer Research Center (CNIO) has contributed this week to clearing up those unknowns by describing one of the key mechanisms that explain reprogramming. According to their data, published in the journal Science, when reprogramming occurs in tissue, tissue damage is a relevant factor in reversing the state of cells.
The Yamanaka technique is based on the introduction of a cocktail of four genes called OSKM. The combination of these factors makes it possible for an adult cell, such as a neuron, to revert to an embryonic (or pluripotent) cell and thus to be able to become any other specific cell in the organism.
Until 2013 all attempts in reprogramming had been made in laboratories, in culture plates. But then the Tumor Suppression Group of the CNIO managed to reprogram cells inside a living organism – a transgenic mouse , opening the door, among other things, to a better knowledge of the process.
The continuation of their research has allowed them, in fact, to discover that tissue damage plays a very important role in reprogramming.
When the researchers activated the Yamanaka factors, some of the differentiated cells were damaged. And that damage favored the process of reprogramming neighboring cell that begun with the introduction of the gene cocktail.
The discovery changed since it was considered that the cellular damage caused by OSKM did not play any role in the reprogramming process or even contributed to reduce the effectiveness of the technique.
In particular, CNIO researchers have observed that the ‘injured’ cells secrete signals that are capable of favoring reprogramming in the neighboring cells of the same tissue. These signals, including one molecule, interleukin-6, are key mediators for reprogramming.
To test the relationship between cell damage and reprogramming, CNIO scientists manipulated the process and found that, “extra” damage to lung cells of transgenic mice, ” favored reprogramming” in adjacent cells.
Similarly, they also found that aging, which is associated with higher levels of cellular senescence – a type of alteration by which cells stop dividing even though they do not die – also enhances reprogramming initiated by OSKM factors.
But the finding of CNIO researchers goes far beyond the reprogramming process and could also be useful in understanding the natural regeneration process, which would have important medical implications. The hypothesis is that when a tissue is damaged physiologically, it is possible that the body’s response to regenerate that tissue goes through a process similar to that of reprogramming. According to this theory, the adult cells would back down in their state to increase their regenerative potential and be able to cope with the ‘healing’ of the injured tissue.
The CNIO group will also try to test different pharmacological combinations so that once the essential role of interleukin-6 is known, the process of reprogramming can be further improved and even the process can be started without using the Yamanaka factors .
Yamanaka’s genes are inefficient for inducing reprogramming, so finding new strategies to improve the process would be a great help for research.
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