An African fish holds a secret to tissue regeneration

September 27 () –

A critical component related to speed and response time at the cellular level helps African killifish properly regenerate their tail fin after injury.

By analyzing tissue dynamics during regrowth, scientists at the Stowers Institute for Medical Research found that, in addition to known factors such as how many cells are involved and where they are located, The time cells spend involved in the repair process is also key.

“One of the biggest unsolved mysteries of regeneration is how an organism knows what it has lost after an injury,” he said. in a statement Alejandro Sánchez Alvarado, scientific director of Stowers and author of the work, published in iScience. “Basically, the study points to a new variable in the regeneration equation. If we can modulate the speed and time that a tissue can initiate a regenerative response, this could help us design therapies that can activate and perhaps prolong the regenerative response of tissues that normally would not“.

Shortly after a lesion on the tail of a turquoise killifish (Nothobranchius furzeri), the remaining tissue needs to know how much damage has been done. This tissue must then recruit the appropriate number of repair cells to the site of injury for the appropriate amount of time. Detection of damage, recruitment of repair cells, and timing must work together somehow for the tail to regrow.

“If an animal that can regenerate limbs, such as a tail, loses only a small portion, How do you know not to regenerate an entire new queue but only the missing piece?” said Sánchez Alvarado. To address this question, the team probed different lesion sites on the tail fin of the killifish.

They discovered that skin cells, both near an injury and in distant non-injured regions, launch a genetic program that prepares the entire animal for a repair response. Skin cells at the site of injury then maintain this response and temporarily change their state to modify the surrounding material. called extracellular matrix.

Co-author Augusto Ortega Granillo, a doctoral researcher, compares this matrix to a sponge that absorbs signals secreted from injured tissue that then guides repair cells to get to work. If signals are not received or interpreted correctly, the regeneration process may not restore the original shape and size of the tail.

“We defined very clearly when and where, 24 hours after injury and in the extracellular matrix, the transient cellular state is acting on the fin tissue,” said Ortega Granillo. “Knowing when and where to look allowed us to make genetic alterations and better understand the function of these cellular states during regeneration.”

To investigate whether these different cell states communicate information to the extracellular matrix (the support structure that surrounds cells) during the repair process, the researchers used the CRISPR-Cas9 gene editing technique. They focused specifically on a gene known to modify the extracellular matrix, since they had observed its activation at the beginning of the regeneration response.

By altering the function of this gene, the team aimed to determine its role in transmitting information from cells to the matrix during regeneration.

“These modified animals no longer know how much tissue was lost“said Ortega Granillo. “They still regenerated, but the speed of tissue growth was poor. “This tells us that by changing extracellular space, skin cells tell the tissue how much was lost and how fast it should grow.”

In fact, the speed and amount of regenerated tissue in these genetically modified killifish increased regardless of whether the tail injury was mild or severe. This finding opens the possibility that cellular states that modify the matrix increase regenerative regrowth. If cellular states could be tuned, it could be a way to stimulate a more robust regeneration response.

From an evolutionary perspective, understanding why certain organisms excel at regeneration while others, such as humans, have limited regenerative capabilities is a driving force in the field of regenerative biology. By identifying general principles in organisms with high regenerative capacity, the researchers aim to Potentially apply this knowledge to improve regeneration in humans.