Maintenance of Mammalian Stem Cell States by Honeybee Royalactin

Royal Jelly (RJ) is the queen-maker for the honeybee Apis mellifera, and has documented cross-species effects on longevity, fertility, and regeneration in mammals. We describe novel wound healing and stemness maintenance activities for Royalactin, the major protein component in RJ, in mice and in embryonic and post-natal stem cells, respectively. Royalactin activates a pluripotency gene regulatory network through control of chromatin dynamics to affect a phenotype that mimics ground state pluripotency. We also identified, through a haploid genetic screen, heparan sulfate proteoglycans as the major cell surface binding partners for Royalactin in mammalian cells, and demonstrate important functional interactions between Royalactin and well known pluripotency-regulating pathways. Thus, Royalactin can maintain cellular identity through affecting the dynamic state of stem cells. Each experiment was performed in at least biological duplicate with input or other controls when appropriate.