(T1337) STRAIGHTFORWARD IN VITRO EMBRYO MODEL BY CONFLICTING TRANSCRIPTIONAL DETERMINANTS OF EARLY MOUSE EXTRAEMBRYONIC AND EMBRYONIC DEVELOPMENT THROUGH INCREASED STAT3 SIGNALING
PhD Student Guangzhou Laboratory Guangzhou, China (People's Republic)
Abstract: The segregation of inner cell mass (ICM) and trophectoderm (TE) marks the first cell fate defining milestone in mouse early embryogenesis. The ICM gives rise to embryo proper, while TE conduct implantation via direct interaction with the uterus and forms the fetal portion of the placenta. During early embryo development, ICM and TE derivatives exhibit dynamic regulative interactions and inter-conversion, where TE derived lineages play a pivotal role in tuning embryonic development. However, the suboptimal research approaches and ethical concerns hinder the feasibility to dynamically monitor these interactions from pre-implantation to post-implantation stages. Although several studies have shed light to the field by generation of in vitro embryo model mimicking key developmental events, these embryo models mostly rely on the mixture of cell types cultured in distinct culture conditions and often fail to sustain TE-derived lineages or progress beyond the pre-implantation stage. Here we report a straightforward mouse embryo model generated exclusively via increased JAK/STAT3 signaling in single sourced embryonic stem cells (ESCs). Through modulating JAK/STAT3 activation level, ESCs efficiently reprogram into intermediates co-expressing conflicting cell fate determinants OCT4, CDX2 and GATA6. The intermediates exhibit molecular features of both ICM and TE lineages, which further undergo spontaneous cell fate determination in petri-dish. The resulting ICM and TE -like cells share synchronized developmental status where transcriptomic analysis confirms the activation of pre-implantation TE-specific signaling pathways. Upon aggregation, the intermediates can self-assemble into a pre-implantation embryo-like structure containing both embryonic and extraembryonic tissues in vitro with high efficiency. This model holds great developmental potential, exhibiting strong morphological and molecular interaction resemblance to a gastrulating embryo upon prolonged culture, with coordinating embryonic and extraembryonic compartments. Our embryo model provides a robust, single-cell-derived system to recapitulate synchronized early embryo development, offering a simplified yet effective platform to study critical embryogenesis events in vitro.
