Many organisms possess the ability to regenerate damaged or lost tissues, yet the reasons why certain species excel in this aspect while others do not remains unclear. Recent research led by molecular biologists Alexander Stockinger, Leonie Adelmann, and Florian Raible from the Max Perutz Labs at the University of Vienna has made a significant advancement in understanding this phenomenon. Their study sheds light on the molecular processes behind regeneration in marine worms, enhancing our comprehension of how cells can naturally reprogram themselves. The findings have been published in the journal Nature Communications.
The capacity to regenerate, whether at the level of individual cells, organs, or complicated tissues, is vital for all living organisms. The human body also undergoes regeneration, wherein dead cells are replaced with newly generated ones. For instance, this occurs in the intestinal lining and the liver. However, some animals possess far greater regenerative capabilities. Annelids, like Platynereis dumerilii, can completely regenerate sections of their posterior body following damage. Until now, the molecular processes governing this regeneration were largely unexplored. The latest research by molecular biologist Florian Raible and his team at the Max Perutz Labs has revealed new insights into this subject, providing a deeper understanding not just of biology but also of how cells naturally reprogram themselves.
Regeneration in marine worms is managed by a distinct growth zone that contains unique stem cells. When these cells divide, they lead to the formation of new segments (body parts). But what occurs if this growth zone is compromised due to an injury? In their recent study, lead authors Alexander Stockinger and Leonie Adelmann, along with Raible’s research team, explored the molecular mechanisms that facilitate the renewal of a lost growth zone, allowing the marine worms to generate new segments once more. A notable aspect of Platynereis dumerilii is that, unlike other species, its regeneration does not depend on pre-existing stem cells. Rather, differentiated cells can undergo a process called dedifferentiation following the removal of the growth zone. “This means that these differentiated cells revert to a stem cell-like state within just a few hours to quickly reconstruct a new growth zone,” explains Leonie Adelmann, one of the primary authors of the study.
The researchers also discovered that the gene expression in these newly generated stem cells differs from that of their precursor cells. “Interestingly, factors related to the transcription factors Myc and Sox2, which are also utilized in modern medicine to convert differentiated human cells to stem cells, are involved in this process as well,” states Alexander Stockinger, the other lead author of the research.
“The idea of dedifferentiation was proposed over six decades ago, but at the time, researchers lacked the necessary tools to validate this concept. We have now developed tools to explore dedifferentiation at a molecular level and compare it to the so-called ‘reprogramming’ in modern medicine. This lays a strong foundation for future research,” summarizes Florian Raible, head of the research group at the University of Vienna.
One innovative approach the scientists employed was the use of single-cell RNA sequencing to investigate cell states. This method generated a novel dataset for examining tissue regeneration. “Single-cell transcriptomics allows us to identify different cell types and their states and observe how they react to the loss of body parts at an individual level. In our research, we also combined this method with fluorescent labeling data provided by our colleagues in France, which helped identify which tissues originate from specific stem cells,” explains Stockinger. “We identified at least two distinct stem cell populations—one responsible for regenerating tissues like the epidermis and neurons, and another that forms muscles and connective tissue,” adds Adelmann.
