| 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
|
| Resource |
| DNA material |
CSII-EF-MCS (RDB04378)
pCMV-VSV-G-RSV-Rev (RDB04393)
pCAG-HIVgp (RDB04394) |
