卵子介导细胞重编程的基础与应用研究

Basic and applied studies of oocyte-mediated reprogramming

细胞重编程一般是指将分化细胞转变成全能性胚胎或多能性细胞的过程,是研究发育和分化的重要手段,为再生医学、疾病个体化治疗及药物筛选等提供了巨大的应用前景。诱导细胞重编程的方法有多种,如细胞培养、卵子介导的核移植(nuclear transfer)、细胞融合、山中伸弥因子介导的诱导多能干细胞(i PSC)技术等。以国家自然科学基金重大研究计划为依托,李劲松课题组围绕着卵子介导的细胞重编程领域开展了系统的研究,取得了一系列突破性的进展:完善了卵子介导的核移植体系;建立精子和卵子来源的"类精子"的单倍体胚胎干细胞系和半克隆技术;建立人和猴子的孤雌单倍体胚胎干细胞系;卵子介导的重编程与i PSC技术比较揭示影响重编程的重要因子;建立卵子介导遗传疾病治疗的策略。现主要对卵子介导细胞重编程的基础与应用研究的原创性实验成果进行综述,并展望未来关注的重点研究方向。

Cell reprogramming, which generally refers to the conversion of differentiated cells into totipotent embryos or pluripotent cells, offers exciting promises in basic and applied research. Adult cells can be successfully reprogrammed into pluripotent stem cells through various ways, including culture-induced reprogramming, oocytes- mediated nuclear transfer （NT）, cellular fusion and induced pluripotent stem cell （iPSC） by expression of Yamanaka factors. Supported by grants from the Major Research Program of the National Natural Science Foundation of China, we have carried out a systemic research focusing on oocyte-mediated reprogramming and obtained the following achievements, including optimization of the oocyte-mediated nuclear transfer, establishment of haploid embryonic stem cell （haESCs） lines that can be used as the sperm replacement for producing health semicloned mice （so-called semicl0ned technology）, establishment of monkey and human parthenogenetic haESCs （PG- haESCs） that allow large-scale genetic screening, revealing that the important reprogramming factor involved in oocyte-mediated reprogramming can be used for generation of iPS cells with high developmental potential, and establishment of the oocyte-mediated gene therapeutic strategies. In this review, we summarize our original works about basic and applied studies of oocyte-mediated reprogramming, and discuss our future research interests.