Researchers from the University of Vienna have identified potential candidates for multipotent stem cells in the sea anemone for the first time. These stem cells are regulated by evolutionary highly conserved genes, which in humans are usually only active in the formation of egg and sperm cells, but give ancient animal phyla such as cnidarians a high degree of regenerative capacity to even escape aging. The findings could provide insights into human aging research.

The study was published in Science Advances in an article titled, “Nanos2 marks precursors of somatic lineages and is required for germline formation in the sea anemone Nematostella vectensis,” and was led by Ulrich Technau, PhD, a professor from the University of Vienna.

“In animals, stem cell populations of varying potency facilitate regeneration and tissue homeostasis,” the researchers wrote. “Notably, germline stem cells in both vertebrates and invertebrates express highly conserved RNA binding proteins, such as nanos, vasa, and piwi. In highly regenerative animals, these genes are also expressed in somatic stem cells, which led to the proposal that they had an ancestral role in all stem cells. In cnidarians, multi- and pluripotent interstitial stem cells have only been identified in hydrozoans. Therefore, it is currently unclear if cnidarian stem cell systems share a common evolutionary origin.”

While humans and most vertebrates can only regenerate parts of certain organs or limbs, other animal groups have far stronger regeneration mechanisms. This ability is made possible by pluripotent or multipotent stem cells, which can form (differentiate) almost all cell types of the body. The sea anemone Nematostella vectensis is also highly regenerative: it can reproduce asexually by budding and also shows no signs of aging, which makes it an interesting subject for stem cell research. However, researchers have not yet been able to identify any stem cells in these animals.

Using single-cell genomics, Technau and his team could identify cells of a complex organism based on their specific transcriptome profiles and determine from which stem cells they have developed. “By combining single-cell gene expression analyses and transgenesis, we have now been able to identify a large population of cells in the sea anemone that form differentiated cells such as nerve cells and glandular cells and are therefore candidates for multipotent stem cells,” explained first author Andreas Denner from the University of Vienna. They have remained undiscovered until now due to their tiny size.

These potential stem cells express the evolutionarily highly conserved genes nanos and piwi, which enable the development of germ cells (sperm and egg cells) in all animals, including humans. By specifically mutating the nanos2 gene using the CRISPR gene scissors, the scientists were also able to prove that the gene is necessary for the formation of germ cells in sea anemones. It has also been shown in other animals that this gene is essential for the production of gametes.

By identifying multipotent stem cells regulated by highly conserved genes, the research team led by the University of Vienna has provided a glimpse into the genetic blueprint that enables these ancient creatures to potentially escape aging.

In humans, these genes are active during the formation of reproductive cells, but in sea anemones, they play a crucial role in continuous regeneration and potential immortality. By studying how these genes function to maintain and regulate stem cells in sea anemones, researchers can gain insights into enhancing stem cell longevity and regenerative capacities in humans, which could lead to potential treatments for age-related diseases.

In future studies, Technau and his team want to investigate which special properties of the sea anemone’s stem cells are responsible for its potential immortality.

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