Embryonic origins of adult pluripotent stem cells discovered

Stem cells are a biological wonder. They can repair, restore, replace, and regenerate cells. In most animals and humans these cells are limited to regenerating only the cell type they are assigned to. So, hair stem cells will only make hair. Intestine stem cells will only make intestines. But, many distantly-related invertebrates have stem cell populations that are pluripotent in adult animals, which means they can regenerate virtually any missing cell type, a process called whole-body regeneration.

Even though these adult pluripotent stem cells (aPSCs) are found in many different types of animals (such as sponges, hydras, planarian flatworms, acoel worms, and some sea squirts) the mechanism of how they are made is not known in any species.

In a new study in Cell researchers in the Department of Organismic and Evolutionary Biology at Harvard University have identified the cellular mechanism and molecular trajectory for the formation of aPSCs in the acoel worm, Hofstenia miamia.

H. miamia, also known as the three-banded panther worm, is a species that can fully regenerate using aPSCs called “neoblasts.” Chop H. miamia into pieces and each piece will grow a new body including everything from a mouth to the brain. Senior author Professor Mansi Srivastava collected H. miamia in the field many years ago because of its regenerative ability. Once back in the lab, H. miamia began to produce many embryos that could easily be studied.

A previous study by Srivastava and co-author postdoctoral researcher Lorenzo Ricci developed a protocol for transgenesis in H. miamia. Transgenesis is a process that introduces something into the genome of an organism that is not normally part of that genome. This method allowed lead author Julian O. Kimura (PhD ’22) to pursue his question of how these stem cells are made.

“One common characteristic among animals that can regenerate is the presence of pluripotent stem cells in the adult body,” said Kimura. “These cells are responsible for re-making missing body parts when the animal is injured. By understanding how animals like H. miamia make these stem cells, I felt we could better understand what gives certain animals regenerative abilities.”

There are some unifying features of these stem cell populations in adult animals such as the expression of a gene called Piwi. But in no species so far has anyone been able to figure out how these stem cells are made in the first place. “They’ve mostly been studied in the context of adult animals,” said Srivastava, “and in some species we know a little bit about how they might be working, but we don’t know how they are made.”

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