Honey Bee Protein Helps Keep Stem Cells Youthful

To make new queens for their colonies, honey bees use royal jelly to turn several female worker bee larvae into potential candidates, and the last one standing after a battle-royale type event is the new queen. Now, according to a team of researchers from Stanford University’s School of Medicine, a protein in mammals has been found to have a similar structure to that of royal jelly’s active component, and it acts as a type of “fountain of youth” for embryonic stem cells—at least for those in the mice used in a recent study. The protein allows cells to stay pluripotent, meaning they could turn into any cell within the body, during conditions that typically trigger the cells to turn into more specialized cells.

This unexpected discovery, saying plenty about royal jelly’s components, has revealed new pathways for pluripotency and could allow for new, original ways of keeping stem cells “young” until they’re needed for therapies in the future. According to Dr. Kevin Wang, an assistant dermatology professor with Stanford and a senior author for this study, published by Nature Communications, “The DNA sequence of royalactin, the active component in the jelly, is unique to honey bees. Now, we’ve identified a structurally similar mammalian protein that can maintain stem cell pluripotency.”

The reasons behind why strict royal jelly diets lead to large, fertile queens rather than lowly worker bees have remained elusive to researchers like Dr. Wang, who has wondered specifically how so similar genomes result in such extreme differences between queen bees and worker bees. “I’ve always been interested in the control of cell size,” says Wang, “and the honey bee is a fantastic model to study this. These larvae all start out the same on day zero, but end up with dramatic and lasting differences in size.” Wang’s team focused on the protein royalactin, previously suggested as being royal jelly’s active ingredient, and they applied it to embryonic stem cells in mice and studied responses by the cells.

Wang said, “For royal jelly to have an effect on queen development, it has to work on early progenitor cells in the bee larvae. So, we decided to see what effect it had, if any, on embryonic stem cells.” When they’re grown in a lab, embryonic stem cells usually try abandoning the stem cell state to become specialized cells. Researchers need to add molecules that prevent this differentiation from happening into the environment where the cells are grown. Surprisingly, adding royalactin prevented the stem cells from becoming specialized and differentiating, even without other molecular inhibitors.

Further experiments showed the stem cells treated with royalactin exhibited profiles like those grown with inhibitors, producing proteins linked to pluripotency while suppressing proteins crucial for differentiation. However, this response by a mammal’s cells confused Wang’s team, as mammals don’t produce royalactin. That’s when they found NHLRC3, a protein in mammals that forms a structure like royalactin and is produced in early embryonic development by all animals. Given its ability to maintain pluripotency in embryonic cells like royalactin, Wang’s team renamed it Regina, or “queen” in Latin. “It’s fascinating. Our experiments imply Regina is an important molecule governing pluripotency and the production of progenitor cells that give rise to the tissues of the embryo. We’ve connected something mythical to something real.”