多能干细胞向雄性生殖细胞定向分化的研究进展

Research progress in differentiation of pluripotent stem cells to male germ cells

生殖健康是生命科学领域关注的核心之一,各种原因所致男性不育亟待解决,然而由于伦理限制等原因,缺少合适的具有人类遗传背景的研究模型开展研究。胚胎干细胞(ESCs)和诱导多能干细胞(iPSCs)均属于多能干细胞,具有多向分化潜能。一方面,可利用ESCs/iPSCs向生殖细胞分化的模型研究人类生殖细胞的发育规律,另一方面,在此基础上,可建立带有人类疾病遗传背景的iPSCs模型,体外诱导其向雄性生殖细胞分化,利用该模型研究男性不育的发病机制。由于精子在体内的形成遵循一定规律,体外环境中不同发育阶段的生殖细胞在不同诱导因子作用下才可稳定地往下一阶段定向分化,因此,诱导ESCs/iPSCs向雄性生殖细胞方向分化时,诱导因子的种类和加入时间的选择应根据生殖细胞的体内发育特征而定,并且在诱导的不同阶段循序加入,以此模拟精子在体内的形成过程,进而更好地研究男性不育的发病机制。本文将对多能干细胞向雄性生殖细胞定向分化的常用诱导因子及存在问题和展望进行综述,为相关研究的开展提供借鉴。

Reproduction is one of the focuses in the field of life science and male infertility is still an unmet medical condition.However,due to ethical restrictions,there is a lack of suitable research models with human genetic background for the study of male infertility.Embryonic stem cells(ESCs)and induced pluripotent stem cells(iPSCs)are both pluripotent stem cells with multi-lineage potentials including differentiating into male germ cells.These research models could not only be applied to study the normal development of human germ cells,but also could be applied to study the pathogenesis of male infertility.Since the formation of sperm in vivo follows certain temporal and spatial regulation,in vitro germ cell differentiation from ESCs/iPSCs could be obtained through sequential supplementation of factors simulating the formation of sperm in vivo.In this review,we intend to summarize the common inducers for differentiating ESCs/iPSCs into male germ cells at developmental stage,as well as discussing the existing problems and prospects for the research of male infertility.