Tyrosine sulfation is a widespread posttranslational modification in mammals and is known to influence protein function and signaling. However, its functio

Human stem cell-based embryo models (hereafter referred to as embryo models) are a rapidly evolving field at the intersection of developmental biology and bioengineering. In this review, we examine design principles, material systems, and engineering approaches that enable the construction of models arising from pluripotent stem cells. We consider how three-dimensional environments, synthetic hydrogels, and spatiotemporal modulation of morphogenetic signals guide self-organization. Together, these factors enable the recapitulation of stages from blastocyst formation to early organogenesis. We then discuss opportunities of these engineered systems in disease modeling and developmental toxicity screening. We also address the scaling issues and biomanufacturing limitations that must be overcome to enable standardized, high-fidelity production.

The post-implantation phase of mammalian development is crucial yet challenging to study due to ethical and technical constraints, particularly in humans. Recent revolutionary advances in extended in vitro culture systems for mammalian embryos now offer unprecedented windows into this developmental “black box”. This review synthesizes how these platforms, alongside stem cell-derived embryo models, are transforming our ability to model early human development in a dish. We detail the technological evolution from two-dimensional (2D) to three-dimensional (3D) cultures that support mouse, non-human primate, and human embryos through key stages of implantation and gastrulation, recapitulating events like lineage specification and axial patterning. Furthermore, we explore how these models serve as powerful tools for investigating the etiology of early pregnancy failure, screening for developmental toxicity of pharmaceuticals, and deciphering the molecular pathogenesis of birth defects. By bridging fundamental embryology with clinical and pharmacological applications, these innovative models herald a new era in biomedical research, holding significant promise for advancing reproductive medicine and regenerative strategies.

Zygotic genome activation (ZGA) is a pivotal event during early mammalian embryonic development and is regulated by multiple molecular factors. In mice, previous studies have demonstrated that long non-coding RNAs (lncRNAs) and transposable elements (TEs) participate in the regulation of this process. However, the functional roles of TEs-associated lncRNAs in porcine ZGA remain largely unknown. In this study, we identified a previously unannotated lncRNA associated with a SINE transposable element sequence in porcine parthenogenetically activated embryos, which we named LincSAKP. LincSAKP exhibited peak expression at the 8-cell stage, coinciding with ZGA, was predominantly localized in the nucleus, and lacked protein-coding potential. Functional analyses demonstrated that depletion of LincSAKP resulted in developmental arrest at the 8-cell stage, accompanied by reduced chromatin accessibility, impaired nascent transcription, and aberrant expression of multiple ZGA marker genes and transcription factors. Transcriptomic analysis combined with rescue experiments identified EP300 as a critical downstream target of LincSAKP. Notably, Depletion of either LincSAKP or EP300 impairs histone H3K27ac modification. EP300 overexpression effectively alleviated the developmental defects caused by LincSAKP depletion. Collectively, our findings identify EP300 as a downstream mediator of LincSAKP in regulating zygotic genome activation, providing insights into the functional network of SINE-associated lncRNAs during parthenogenetically activated early embryonic development. This study expands our understanding of the functional roles of TE-associated non-coding RNAs in early embryonic development and provides a potential theoretical basis for improving the efficiency of in vitro culture of porcine embryos.