Pyruvate metabolism modulates cell fates in naïve human pluripotent stem cell culture and blastoid formation. A study of Zhao et al.

In this study, we applied two different single-cell transcriptome analysis methodologies to obtain dynamic single-cell transcriptome data during whole process of hESC primed-to-naïve conversion. Our analysis uncovered two sequential cell fate decision events, which both took place within the first 6 days of the conversion. The two cell fate bifurcations determined the choices between survival and death as well as between naïve pluripotency and extra-embryonic lineage-like fates, respectively. Notably, pyruvate-related metabolism was identified as a pivotal factor in regulating the cell fate determinations of both bifurcations. Building on these findings, we not only optimized the nhPSC derivation conditions but also achieved a more homogeneous culture of mature nhPSCs, addressing the prior limitations in induction and culture. Moreover, we successfully enhanced the cavitation efficiency during human blastoid formation through adjusting the lineage composition. These results would enrich our understanding of the cell fate trajectory involved in the conversion of phPSCs to nhPSCs and facilitate nhPSC application and human blastoid formation.