GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE282nnn/GSE282953/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE282953GEOGSEfalseEnhanced organogenesis and placenta development in metabolically reprogrammed blastoids derived from mouse naïve ESCs [scRNA-seq]Blastoids recapitulate key morphogenetic events during preimplantation and early post-implantation development. However, their long-term post-implantation development is limited in vivo and in vitro. Here, we report that a chemical cocktail, Lnαnv, enables efficient formation (an average of 70 %) of blastoids (ESC-blastoids) from conventional mouse embryonic stem cells (ESCs) through metabolic reprogramming, in contrast to the control (efficiency at 6%). These ESC-blastoids not only resembled blastocysts in morphology and cell lineage allocation, but exhibited similar metabolic profile and Cdx2-high expressing trophectoderm-like (TE-like) cells. Further increasing totipotency of ESCs by small molecules pladienolide B (PlaB) combined with crotonic acid (CA) enhanced developmental potential of the derived blastoids (PC-blastoids), capable of generating E10.5-like gonad tissues, a beating heart-like structure and blood vessels under specific in vitro culture systems. Single-cell RNA-sequencing revealed that Lnαnv-induced PC-blastoids were transcriptionally and metabolically similar to natural blastocysts. Furthermore, these PC-blastoids generated TE-like cells that more closely resemble the true TE, exhibiting increased Cdx2+ cells and Cdx2 expression levels compared to other reported blastoids, which may contribute to their enhanced developmental potential. Upon transfer, the blastoids developed into E8.5 stage with placenta development in vivo. Therefore, by simulating the metabolism reprogramming and enhancing the totipotency of ESCs for blastoid induction, we produced blastoids with highly enhanced development potential from ESCs, extending post-implantation development both in vitro and in vivo.2026/09/02GSE282953GSM8653478GSM8653476GSM8653477GSM8653474GSM865347524247282953Mus musculus