目的　研究真皮来源成体多能干细胞体外恶性转化现象及其相关机制。方法　对分离的真皮多能干细胞克隆体外进行连续传代培养 ,观察其生长性状的改变 ,通过裸鼠皮下接种实验观察其是否恶性转化 ;应用基因芯片技术比较转化前后细胞基因表达谱的改变。结果　经过长期体外连续传代培养后 ,真皮多能干细胞可发生恶性转化 ,在裸鼠体内形成肉瘤样组织 ;基因芯片技术检测显示 ,转化后细胞仍表达多种类型细胞特异性基因的转录子 ,提示其仍具有多向分化的潜能 ;但转化后细胞多种增殖相关基因的表达升高 ,代谢反应酶类基因表达升高 ,生长因子和受体的表达下调 ,符合肿瘤细胞的特征 ;c ki ras基因及其相关信号分子的表达上调可能在转化过程中起重要作用 ;初步筛选鉴定了一个与干细胞增殖调控相关的候选基因。结论　体外长期连续传代培养可诱发真皮多能干细胞的恶性转化 ,深入研究这一过程的分子机制对干细胞的安全应用和肿瘤的发生机制均具有研究意义 Objective To study the malignant transformation of dermal derived adult pluripotent stem cells in vitro and its related mechanisms. Methods The isolated cloned pluripotent stem cells were subcultured in vitro and their growth traits were observed. The malignant transformation of the pluripotent stem pluripotent stem cells was observed by subcutaneous inoculation in nude mice. The changes of gene expression profiles were compared using gene chip technique. Results After long-term continuous culture in vitro, the dermal pluripotent stem cells could undergo malignant transformation and form sarcomatoid tissues in nude mice. Gene chip technology showed that the transformed cells still expressed many cell-specific gene transcripts, suggesting that Which still has the potential of multidirectional differentiation. However, after the transformation, the expression of many proliferation-related genes increased, the expression of metabolic reaction enzymes increased, and the expression of growth factors and receptors decreased, which accorded with the characteristics of tumor cells. C ki ras Upregulation of genes and their related signaling molecules may play an important role in the transformation process. A preliminary screening and identification of a candidate gene related to stem cell proliferation regulation. CONCLUSION: Long-term continuous subculture in vitro can induce the malignant transformation of dermal pluripotent stem cells. It is of great significance to study the molecular mechanisms of this process for the safe application of stem cells and the mechanism of tumorigenesis