ABSTRACT During early mammalian embryogenesis, totipotent zygotes and early blastomeres undergo extensive post‐transcriptional regulation during the establishment of the first cell lineages; however, the functional contribution of alternative splicing to embryonic compaction and blastulation remains poorly understood. Here, we show that SF3B1, a core component of the spliceosome, is upregulated from the 4‐cell stage and mediates highly dynamic splicing programs. Depletion of SF3B1 results in developmental arrest at the morula stage, accompanied by widespread transcriptomic dysregulation characterized by aberrant expression of transcription factors that impede pluripotency transition. Alternative splicing analysis further identifies that aberrantly spliced transcripts were significantly enriched in genes involved in cell cycle regulation, such as Cdk11b and Ccnb1. Importantly, we demonstrate that SF3B1 undergoes intrinsic, IDR‐driven liquid‐liquid phase separation both in vitro and in vivo, forming nuclear condensates in oocytes and early embryos, which is essential for successful development to the blastocyst stage. Together, our findings reveal that phase separation mediated SF3B1 splicing activity is a critical regulator of early mouse embryonic development.
Kang Zhao, Ting-Yu Han, Yan-Li Cheng et al.· Advancement of science· 0 citations
Understanding the impact of spaceflight on human reproduction is critical for interplanetary exploration, yet technical barriers have limited direct studies of germ cell biology in orbit. Here, we utilized an automated bioreactor that supported long-term differentiation of human embryonic stem cells into human induced primordial germ cells (hiPGCs), human induced ovarian follicles (hiOFs), and human induced spermatogonial stem cells (hiSSCs) aboard spacecraft. Integrated real-time imaging, programmable medium perfusion, and in situ preservation enabled time-resolved multi-omics analysis. During missions on China’s Tianzhou-1 and Tianzhou-6 spacecraft, spaceflight reduced hiPGC specification efficiency by approximately 50% and suppressed hiSSC proliferation by 26%. Transcriptome-translatome coordination revealed cell-type-specific dysregulation of extracellular matrix organization, microtubule dynamics, and lipid metabolism. Whole-exome sequencing and DNA methylome analysis demonstrated preserved genomic integrity despite these functional perturbations. These findings provide direct evidence that spaceflight perturbs human germ cell development and establish a scalable framework for monitoring cellular adaptation during deep-space missions.
Ying Li, Hui Gao, Jie Xiong et al.· Science Advances· 0 citations
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