RRC ID 77520
Author Hayashi Y, Tando Y, Ito-Matsuoka Y, Ikuta K, Takehara A, Morino K, Maegawa H, Matsui Y.
Title Nutritional and metabolic control of germ cell fate through O-GlcNAc regulation.
Journal EMBO Rep
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.
Volume 24(11)
Pages e56845
Published 2023-11-6
DOI 10.15252/embr.202356845
PMID 37842859
PMC PMC10626443
MeSH Acetylglucosamine* / chemistry Acetylglucosamine* / metabolism Epigenesis, Genetic Gene Expression Regulation Germ Cells / metabolism Humans Infant, Newborn Protein Processing, Post-Translational Signal Transduction* / physiology
IF 7.497
DNA material CSII-EF-MCS (RDB04378) pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394)