诱导多能干细胞（iPSC）为再生医学带来巨大的曙光，iPSC来源的NK细胞（iNK）成为近年抗肿瘤领域备受瞩目的焦点。但iPSC分化为NK细胞所需时间长，程序繁琐，如何高效制备iNK产品，探索进行基因改造的时机及功能评估，仍然有待进一步研究。我们前期工作中发现一条全新的多能性相关lncRNA，命名为Oplr16，可通过表观遗传学机制提高iPSC的重编程效率，并且形成的Oplr16-iPSC多能性强于传统iPSC，细胞处于原始态，在诱导分化过程中，更趋向于分化为血液细胞。本项目拟利用Oplr16诱导重编程，形成Oplr16-iPSC，高效分化为iNK。深入研究Oplr16促进干细胞向造血细胞分化的机制，并在重编程及分化的各阶段进行基因编辑，探索基因改造的时机及NK细胞功能评估。尝试以lncRNA为媒介达到操纵和控制细胞命运，推动iPSC向NK细胞的临床转化，为肿瘤的免疫治疗提供新策略。

Induced pluripotent stem cells (iPSC) have brought great dawn to regenerative medicine. IPSC-derived NK cells (iNK) have attracted much attention in the field of antitumor in recent years. However, it takes a long time for iPSCs to differentiate into NK cells, the procedures are cumbersome. How to efficiently prepare iNK products, explore the timing and functional evaluation of genetic modification, remains to be further studied. In our previous work, we discovered a new pluripotency-related lncRNA named Oplr16, which can improve the reprogramming efficiency of iPSC through epigenetic mechanisms.Furthermore, Oplr16-iPSC is more pluripotent than traditional iPSC, it is at naïve status. Excitingly, in the process of differentiation, it tends to differentiate into blood cells. This project intends to use Oplr16 to induce reprogramming to form Oplr16-iPSC, which will efficiently differentiate into iNK. In-depth study of the mechanism by which Oplr16 promotes the differentiation of stem cells into hematopoietic cells, gene editing at various stages of reprogramming and differentiation, exploring the timing of genetic modification and NK cell function evaluation. Try to use lncRNA as a medium to achieve manipulation and control of cell fate, promote the clinical transformation of iPSC to NK cells, provide new strategies for tumor immunotherapy.