Pankammoon Peachanika, Salinas Marvin Bryan Segundo, Thitaram Chatchote, Sathanawongs Anucha
Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai 50100, Thailand.
Department of Basic Veterinary Sciences, College of Veterinary Science and Medicine, Central Luzon State University, Science City of Muñoz 3120, Nueva Ecija, Philippines.
Int J Mol Sci. 2025 Apr 2;26(7):3310. doi: 10.3390/ijms26073310.
For nearly three decades, interspecies somatic cell nuclear transfer (iSCNT) has been explored as a potential tool for cloning, regenerative medicine, and wildlife conservation. However, developmental inefficiencies remain a major challenge, largely due to persistent barriers in nucleocytoplasmic transport, mitonuclear communication, and epigenome crosstalk. This review synthesized peer-reviewed English articles from PubMed, Web of Science, and Scopus, spanning nearly three decades, using relevant keywords to explore the molecular mechanisms underlying iSCNT inefficiencies and potential improvement strategies. We highlight recent findings deepening the understanding of interspecies barriers in iSCNT, emphasizing their interconnected complexities, including the following: (1) nucleocytoplasmic incompatibility may disrupt nuclear pore complex (NPC) assembly and maturation, impairing the nuclear transport of essential transcription factors (TFs), embryonic genome activation (EGA), and nuclear reprogramming; (2) mitonuclear incompatibility could lead to nuclear and mitochondrial DNA (nDNA-mtDNA) mismatches, affecting electron transport chain (ETC) assembly, oxidative phosphorylation, and energy metabolism; (3) these interrelated incompatibilities can further influence epigenetic regulation, potentially leading to incomplete epigenetic reprogramming in iSCNT embryos. Addressing these challenges requires a multifaceted, species-specific approach that balances multiple incompatibilities rather than isolating a single factor. Gaining insight into the molecular interactions between the donor nucleus and recipient cytoplast, coupled with optimizing strategies tailored to specific pairings, could significantly enhance iSCNT efficiency, ultimately transforming experimental breakthroughs into real-world applications in reproductive biotechnology, regenerative medicine, and species conservation.
近三十年来，种间体细胞核移植（iSCNT）一直被探索作为克隆、再生医学和野生动物保护的一种潜在工具。然而，发育效率低下仍然是一个主要挑战，这在很大程度上是由于核质运输、线粒体核通讯和表观基因组串扰方面存在持续障碍。本综述综合了来自PubMed、科学网和Scopus的近三十年经过同行评审的英文文章，使用相关关键词来探索iSCNT效率低下背后的分子机制和潜在的改进策略。我们强调了最近的研究结果，这些结果加深了对iSCNT中种间障碍的理解，强调了它们相互关联的复杂性，包括以下几点：（1）核质不相容可能会破坏核孔复合体（NPC）的组装和成熟，损害必需转录因子（TFs）的核运输、胚胎基因组激活（EGA）和核重编程；（2）线粒体核不相容可能导致核DNA和线粒体DNA（nDNA-mtDNA）不匹配，影响电子传递链（ETC）组装、氧化磷酸化和能量代谢；（3）这些相互关联的不相容性会进一步影响表观遗传调控，可能导致iSCNT胚胎中的表观遗传重编程不完全。应对这些挑战需要一种多方面的、针对特定物种的方法，该方法要平衡多种不相容性，而不是孤立单一因素。深入了解供体细胞核与受体细胞质体之间的分子相互作用，再加上针对特定配对优化策略，可能会显著提高iSCNT效率，最终将实验突破转化为生殖生物技术、再生医学和物种保护领域的实际应用。
