胰腺癌是恶性程度最高的肿瘤之一，其早期诊断率低，术后复发和死亡率高。近年来，胰腺癌在我国呈快速上升的趋势，目前分别在男性和女性中为致死恶性肿瘤的第六和第七位。大多数胰腺癌患者在被确诊时已发生肿瘤转移，因此研究胰腺癌转移的分子机制，将为其临床治疗以及靶点药物的研发提供重要的理论基础。我们之前的研究表明表观基因组的改变，而非基因组序列的变化，可能才是胰腺癌转移的驱动因素。本项目立足于我们之前的研究结果，拟已建立的胰腺癌转移肿瘤的原代培养细胞系为研究材料，利用单细胞多组学测序技术，在细胞水平上动态的揭示肿瘤细胞群体转移过程中表观基因组的重编程过程：1）描绘肿瘤细胞转移过程中不同细胞亚群的表达谱和表观遗传特征；2）鉴定出在转移过程中受表观调控的重要基因；3）阐明这些候选基因的表观调控分子机制。本项目将不仅能进一步揭示胰腺癌细胞转移的表观遗传调控分子机制，并为胰腺癌的临床治疗提供可能的药物靶标。

Pancreatic cancer is one of the most deadly of all types of cancer. Currently, the early detection of pancreatic cancer is exceedingly difficult and the prognosis is dismal, with only 8% of patients surviving more than 5 years after diagnosis. In China, the incidence of pancreatic cancer has increased rapidly in recent years, and now pancreatic cancer is the sixth leading cause of cancer death in men and the seventh in women. Since most patients will already have metastases at the time of diagnosis, understanding the molecular mechanisms underlying metastasis could help to develop novel diagnostic and therapeutic methods. Our previous study has shown that epigenomic changes, rather than genomic changes, might drive progression and metastasis of pancreatic cancer. In this project, by single-cell multi-omics technology and using epigenomic reprogramming process of distant metastasis under drug (6AN) treatment as model, we aim to reveal the dynamics of epigenomic reprogramming of tumor cell population at single-cell level: 1) to identify tumor cell population structure during reprogramming and characterize the transcriptomic and epigenomic features for each sub-population; 2) to identify candidate genes which may play essential roles in metastasis through epigenetic regulation; 3) to elucidate molecular mechanisms of those candidate genes in detail by functional assays. This projects will not only shed light on the epigenetic mechanisms of metastasis in pancreatic cancer but also could provide potential therapeutic strategies to prevent or combat metastasis.