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Abstract
Royal jelly is the queen-maker for the honey bee Apis mellifera, and has cross-species effects on longevity, fertility, and regeneration in mammals. Despite this knowledge, how royal jelly or its components exert their myriad effects has remained poorly understood. Using mouse embryonic stem cells as a platform, here we report that through its major protein component Royalactin, royal jelly can maintain pluripotency by activating a ground-state pluripotency-like gene network. We further identify Regina, a mammalian structural analog of Royalactin that also induces a naive-like state in mouse embryonic stem cells. This reveals an important innate program for stem cell self-renewal with broad implications in understanding the molecular regulation of stem cell fate across species.
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1 Department of Dermatology, Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA; Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA
2 Department of Dermatology, Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA; Program in Cancer Biology, Stanford University School of Medicine, Stanford, CA, USA
3 Department of Dermatology, Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA
4 Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA
5 The Glenn Laboratories for the Biology of Aging and Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA
6 Department of Developmental Biology, Howard Hughes Medical Institute, Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA
7 Canary Center for Cancer Early Detection, Department of Radiology, Stanford University School of Medicine, Palo Alto, CA, USA
8 Department of Comparative Medicine, Stanford University School of Medicine, Stanford, CA, USA
9 Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA
10 LakePharma, Inc., Belmont, CA, USA
11 R&D Systems, Inc, Minneapolis, MN, USA
12 Department of Dermatology, Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA; Program in Cancer Biology, Stanford University School of Medicine, Stanford, CA, USA; Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA, USA