Epigenetic reprogramming in SCNT embryos: from inefficient remodeling to precision enhancement

Somatic cell nuclear transfer (SCNT) is a unique reproductive engineering technique capable of conferring totipotency onto a somatic cell genome. It holds significant promise for animal germplasm conservation, livestock industry advancement, and biomedical research. Despite successful cloning in many species, the efficiency of mammalian cloning remains low and has seen little progress in recent years. The low viability of cloned animals and the frequent developmental abnormalities observed are widely recognized to be attributed to incomplete epigenetic reprogramming. Recent advances in technology, particularly low-input sequencing methods, have driven new breakthroughs in improving cloning efficiency research in recent years. This review systematically outlines the core and emerging epigenetic barriers in SCNT and provides a comprehensive evaluation of the latest strategies to increase cloning efficiency, including refined epigenetic modulation and genetic regulation. Furthermore, we address the current challenges and future research directions, offering novel insights for studies and practices aimed at enhancing somatic cell cloning efficiency.