摘要
啮齿类和传统的灵长类多能干细胞(pluripotent stem cells,PSCs)在很多方面表现出不同的属性.根据发育阶段、克隆形态、信号依赖、线粒体代谢、嵌合能力、基因表达以及表观遗传等差异,哺乳动物干细胞多能性被分为原始态(Naive)和始发态(Primed)两种状态.啮齿类PSCs表现为Naive特性,而小鼠外胚层干细胞(epiblast stem cells,Epi SCs)和传统的灵长类PSCs表现为Primed特性.体外是否存在灵长类Naive PSCs是当前干细胞研究的一个关键性科学问题,开展非人灵长类PSCs的研究对于解决该问题起到至关重要的作用.最近几项研究通过各自的方法获得了不同的灵长类Naive-like PSCs,这些细胞在很多方面表现出类似于啮齿类PSCs的Naive特性.本文分析了啮齿类和灵长类胚胎发育差异性产生不同PSCs的可能机制,总结了本研究组和其他研究小组在灵长类干细胞多能性方面的研究进展以及原始态(Naive)和始发态(Primed)PSCs自我更新的调控机制差异最后,对灵长类干细胞多能性研究存在的问题进行了分析,对将来的研究重点进行了展望.
Conventional primate pluripotent stem cells（PSCs） display different properties with rodent PSCs. Mammalian PSCs are defined as naive- and primed-PSCs according to their varieties in cellular developmental stage, clone morphology, signaling pathway dependences, mitochondrial metabolism pattern, chimera competence, gene expression profiles and epigenetic states, respectively. Rodent PSCs exhibit the naive features because of their similarities to blastomere of pre-implantation embryos in gene expression profiles, epigenetic state, and their strong chimera competency, whereas mouse epiblast stem cells（Epi SCs） and conventional primate PSCs lack these properties, which is suggestive of their primed state. In the stem cell field, it is a significant scientific issue to investigate whether primate naive PSCs can be captured and cultured in vitro by improving the culture system. Because of ethical issues, we are unable to confirm the naive state of human PSCs by performing chimera function test. Given high similarities between human PSCs and non-human primate PSCs, it is a critical role to perform non-human primate PSC studies. Recently, several studies have reported the generation of naive-like human PSCs and monkey induced PSCs（i PSCs） by using different combinations of pharmacological agents and cytokines. These naive-like primate PSCs share many naive characteristics similar to those of rodent PSCs. Here we analyze the possible mechanisms resulting in the isolation of naive- and primed-PSCs with rodent and primate embryos, summarize the research progress of primate naive pluripotency based on the data from our team and other groups, uncover the different regulation mechanisms controlling naive and primed PSC self-renewal, discuss the current challenges, and predict future research directions emphasis of primate naive PSCs research.
出处
《中国科学：生命科学》
CSCD
北大核心
2015年第12期1203-1213,共11页
Scientia Sinica(Vitae)
基金
国家重点基础研究发展计划(批准号:2012CBA1300)
国家自然科学基金(批准号:31360231)资助
