CD133+肝前体细胞在持续性肝损伤时活化，被广泛视作肝细胞肝癌（HCC）的"肿瘤干细胞"，与HCC发生及多种恶性行为有关。然而，因无法在体内示踪，迄今仍未直接证明CD133+细胞就是HCC的肿瘤起源细胞（TICs）。我们前期研究发现，肝脏特异敲除组蛋白去乙酰化酶3（HDAC3）基因后，小鼠肝细胞持续损伤并丧失再生能力，CD133+细胞则异常活化，以代偿丢失的肝细胞并在部分肝切除后完成肝再生。Hdac3-/-小鼠最终自发HCC，显然与CD133+细胞异常活化密切相关，为研究HCC的TICs提供了极佳模型。HDAC3对维持染色质结构和基因组稳定至关重要，CD133+细胞同样也有HDAC3的缺失，这可能是导致其自身损伤及恶性转化的重要原因。本研究将利用转基因小鼠间异体细胞移植实验，以期直接证明CD133+细胞是HCC的TICs，进而探讨HDAC3介导CD133+细胞损伤及恶性转化的分子机制。

CD133+ hepatic progenitor cells are activated in chronic injured liver, and are widely regarded as the cancer stem cells of HCC. CD133+ cells are closely correlated with the tumorigenesis and development as well as other malignant behaviors of HCC. However, due to the lack of in vivo tracing method,it is still required to directly demonstrate that CD133+ cells are the tumor-initiating cells (TICs) of HCC. In previous study, we found that in the hepatocyte-specific histone deacetylase 3 (HDAC3) gene deficient mice, the hepatocytes are progressively injured and loss the regenerative capacity. CD133+ cells were dramatically activated, therefore, to compensate the loss of hepatocytes and even compensate the liver regeneration after partial hepatectomy. Spontaneous HCC were found in all the Hdac3-/- mice at the age of approximately 10 month. The uncontrolled activation of CD133+ cells are believed to closely relate to the occurrence of the HCC, therefore, this transgenic mouse provides an excellent model for the study of the TICs of HCC. HDAC3 play a crucial role in the maintenace of chromatin structure and genome stability, in Hdac3-/- mice, the deficiency of HDAC3 is also speculated an important cause of the damage and malignant transformation of CD133+ cells. In this study we aim to directly demonstrate that CD133+ cells are the TICs of HCC, using allogeneic cell transplantation experiments, and to explore the molecular mechanism of HDAC3 in mediating the injury and malignant transformation of CD133+cells.