有研究表明正常干细胞可在异常微环境影响下获得遗传学或表观遗传学突变后转化为肿瘤干细胞(CSCs)。我们以往的研究成功将鼠iPS(miPS)细胞在肿瘤微环境中诱导成为具有肿瘤干细胞特性的细胞，即miPS-CSCs细胞(Chen L, et al; 2012)。本课题将对miPS向CSCs转化的分子机制进行研究，我们前期运用基因芯片及qRT-PCR筛选转化前后表达差异显著的基因，发现Dsg2和Dpagt1基因在miPS-CSCs细胞的表达比miPS细胞分别上调4倍和6倍。经查阅相关文献我们提出假说Dsg2和Dpagt1基因可能通过Wnt/β-catenin信号通路参与miPS的恶性转化；下调两基因的表达或抑制Wnt信号通路可以逆转miPS-CSCs的恶性表型。阐明该转化的分子机制为研究CSCs起源、肿瘤发生及基于CSCs为靶点的肿瘤治疗开辟了新路，具有重要的理论及临床意义。

A current view of the cancer stem cells (CSCs) is considered that normal stem cells in abnormal microenviorment may acquire the multiple genetic and epigenetic alterations required to become CSCs that are involved in promoting and maintaining oncogenesis. In our previous study, we originally developed a cell lines named miPS-CSCs with CSCs' characteristics after culturing mouse induced pluripotent stem (miPS) cells under the condition, which is a mimic of carcinoma microenviornment (Chen L, et al; 2012). In this study, to clarify the molecular mechanism of converting miPS to CSCs cells, microarray assessment and qPT-PCR were used to screen the differential expression genes between miPS cells and miPS-CSCs. As the results, the transcripts of Dsg2 and Dpagt1 were up-regulated 4-fold and 6-flod, respectively. Combined with the related literature review, we hypothesized that Dsg2 and Dpagt1 may be involved in converting miPS cells to miPS-CSCs through Wnt/β-catenin signal pathway. Down-regulation of Dsg2 and Dpagt1 expression or inhibition Wnt signal pathway may reverse the malignant phenotype of miPS-CSCs. Whereas the clarification of the molecular mechanism has theory and clinical significance for studying the origin of CSCs, oncogenesis and developing novel and efficacious anti-cancer therapies targeting to CSCs.