Generation of transient totipotent blastomere-like stem cells by short-term high-dose Pladienolide B treatment

ABSTRACT: As an alternative model for study of the dynamic process of early mammalian embryonic development, multiple progresses have been made in using mouse embryonic stem cells (mESCs) to generate embryo-like structure, especially by modifying the starting cells. A previous study has shown that as long as continuously treating mESCs with a low-dose splicing inhibitor, pladienolide B (PlaB), a totipotent state comparable to 2- and 4-cell embryos at molecular levels can be reached. However, these totipotent mESCs mare less proliferative, with the culture time being limited to about 10-15 passages. Here we reported that transiently PlaB-treated mESCs were sufficient for generating a novel type of totipotent-like stem cells from classical mESCs, and these cells were endowed with the ability to differentiate into both embryonic and extra-embryonic cell lineages, we termed them as transient totipotent-like stem cells (TTLCs). Similarly, TTLCs could self-organize to blastoids and recapitulated key preimplantation developmental processes. Transcriptome analysis also showed that TTLC-blastoids bear similarities with mouse E3.5, E4.5 blastocyst and TBLC-blastoids. Moreover, we found that TTLC-blastoids could develop beyond implantation stage, forming egg-cylinder structures both in vivo and in vitro. In summary, our findings provided a rapidly alternative cell type to generate blastoids for the study of early mouse embryogenesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE252206 | GEO | 2025/04/02

REPOSITORIES: GEO