Honeybee Protein May Help To Keep Stem Cells Youthful

The protein causes cells to remain pluripotent meaning they can become any cell within the body under conditions which normally trigger them to develop into specialized cells. This finding will likely fan flames to debated as to regenerative powers of royal jelly, but more importantly reveals new pathways to pluripotency and suggests novel ways to keep stem cells in a state of suspended animation until further needed.

Folklore reveres royal jelly as a form of super medicine in Europe and Asia, DNA sequencing of royalactin which is the active component in the jelly is unique to honeybees, a structurally similar mammalian protein has been identified that can maintain stem cell pluripotency. This discovery was found along the way in a process of wondering how a royal jelly diet could trigger extreme differences between queens and worker bees where Kevin Wang, MD, PhD and colleagues focused on royalactin applying it to mouse embryonic stem cells to study cell responses, as for it to affect development it has to work early on progenitor cells, so they decided to see if it had any effect on embryonic stem cells.

Embryonic stem cells are potent, but when grown in lab settings the fickle cells often abandon stem cell states and differentiate into specialized cells, researchers have devised methods to keep the cells in line by adding molecules that inhibit differentiation to the environment in which the cells grow. The team found addition of royalactin stopped embryonic stem cells from differentiating even in the absence of such inhibitors; the cultured LIF free cells grew for up to 20 generations with the addition.

Additional investigational studies showed the royalactin treated stem cells exhibited gene expression profiles similar to stem cells grown with inhibitors, producing proteins known to be associated with pluripotency while tamping down production of proteins important for differentiation, responses which were confusing as mammals do not make royalactin.

To investigate this even further the team turned to databases that infers the three dimensional structure of proteins, as many proteins work by fitting together with other proteins or biological molecules, making the team wonder if there was a protein in mammals that mimics the shape but not sequence of royalactin. NHLRC3 mammalian protein was found and predicted to form a structure similar to royalactin which is produced early in embryonic development in all animals. NHLRC3 was found to be able to maintain pluripotency in mouse embryonic cells, and caused a similar gene expression pattern in them as those exposed to royalactin; NHLRC3 protein was renamed Regina which is Latin for Queen.

The team plans to investigate whether Regina has therapeutic value in wound healing or cell regeneration in adult animals, and hope their findings will help researchers discover better ways to keep lab grown embryonic stem cells pluripotent. Wang suggests their studies imply Regina is an important molecule governing pluripotency and production of progenitor cells that give rise to tissues of the embryo.