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Publication : Nutritional and metabolic control of germ cell fate through O-GlcNAc regulation.

First Author  Hayashi Y Year  2023
Journal  EMBO Rep Volume  24
Issue  11 Pages  e56845
PubMed ID  37842859 Mgi Jnum  J:342346
Mgi Id  MGI:7548265 Doi  10.15252/embr.202356845
Citation  Hayashi Y, et al. (2023) Nutritional and metabolic control of germ cell fate through O-GlcNAc regulation. EMBO Rep 24(11):e56845
abstractText  Fate determination of primordial germ cells (PGCs) is regulated in a multi-layered manner, involving signaling pathways, epigenetic mechanisms, and transcriptional control. Chemical modification of macromolecules, including epigenetics, is expected to be closely related with metabolic mechanisms but the detailed molecular machinery linking these two layers remains poorly understood. Here, we show that the hexosamine biosynthetic pathway controls PGC fate determination via O-linked beta-N-acetylglucosamine (O-GlcNAc) modification. Consistent with this model, reduction of carbohydrate metabolism via a maternal ketogenic diet that decreases O-GlcNAcylation levels causes repression of PGC formation in vivo. Moreover, maternal ketogenic diet intake until mid-gestation affects the number of ovarian germ cells in newborn pups. Taken together, we show that nutritional and metabolic mechanisms play a previously unappreciated role in PGC fate determination.
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