AI Article Synopsis
- Primordial germ cell (PGC) fate is influenced by complex interactions among signaling pathways, epigenetics, and transcriptional control.
- The study reveals that the hexosamine biosynthetic pathway plays a crucial role in determining PGC fate through a modification called O-linked β-N-acetylglucosamine (O-GlcNAc).
- A maternal ketogenic diet, which lowers O-GlcNAc levels, negatively affects PGC formation and the number of ovarian germ cells in offspring, highlighting the impact of nutrition on germ cell development.
Article Abstract
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 β-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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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10626443 | PMC |
| http://dx.doi.org/10.15252/embr.202356845 | DOI Listing |
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