α-Ketoglutarate promotes trophectoderm induction and maturation from naive human embryonic stem cells.

ABSTRACT: Development and lineage choice are driven by interconnected transcriptional, epigenetic and metabolic changes. Specific metabolites, such as α-ketoglutarate (αKG), function as signalling molecules affecting the activity of chromatin-modifying enzymes. However, how metabolism coordinates cell-state changes, especially in human pre-implantation development, remains unclear. Here we uncover that inducing naive human embryonic stem cells towards the trophectoderm lineage results in considerable metabolic rewiring, characterized by αKG accumulation. Elevated αKG levels potentiate the capacity of naive embryonic stem cells to specify towards the trophectoderm lineage. Moreover, increased αKG levels promote blastoid polarization and trophectoderm maturation. αKG supplementation does not affect gl

SUBMITTER: Van Nerum K 

PROVIDER: S-EPMC12081308 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature