Genome-wide DNA methylation pattern changes in ESC, and EPSC after treated with T09

Embryonic stem cells upon extrinsic induction could self-assemble into blastocyst-like structures. However, the intrinsic regulation of such blastoid forming potential remain to be addressed. We discover that the activity of nuclear receptor subfamily 1, group H, member 2 (Nr1h2) in expanded potential stem cell (EPSC) positively correlates with blastoid efficiency and quality. In addition, Nr1h2 agonist, T0901317, improves natural blastocyst development. Surprisingly, Nr1h2-activated ESC (NrESC) is rewired towards a distinct pluripotency state that is capable of self-organizing into blastoids and contribute to embryonic and extraembryonic lineage. We hypothesize that Nr1h2 activation broadly affects the DNA methylation to rewire ESC state. Indeed, from WGBS data, we observe that genome-wide DNA methylation differences in NrESC or EPSC after treated with T09 . In summary, our study demonstrates a novel Nr1h2-centric regulation of expanded pluripotency. Overall design: Examination of genome-wide DNA methylation in mouse embryonic stem cells and expanded pluripotent stem cells after adding T09 Drug