激光生物学报, 2014, 23 (4): 319, 网络出版: 2015-07-07  

利用化学小分子实现人胚胎干细胞多能性状态的转化

Transformation from Primed to Naive Pluripotent State of Human Embryonic Stem cells by Small Chemical Molecules
作者单位
1 中南大学生命科学学院, 湖南 长沙 410078
2 中南大学生殖与干细胞研究所, 湖南 长沙 410078
摘要
小鼠胚胎干细胞(Embryonic Stem Cells, ESCs)具有两种不同的多能性状态-原始态多能性(naive pluripotency)和始发态多能性(primed pluripotency), 这两种多能性干细胞在形态、自我更新维持条件、基因表达、表观遗传学特征以及单克隆形成率等方面都存在明显差别。传统条件下分离和培养的人胚胎干细胞(human Embryonic Stem Cells, hESCs)生物学特征更接近始发态多能性状态, 需依赖转基因操作才能获得和维持原始态多能性状态。本研究通过在培养体系中添加化学小分子成功地将已建系的始发态多能性hESCs转化为原始态多能性干细胞, 转化后hESCs呈紧密、圆形、隆起的三维克隆结构, 具有两条活化的X染色体, 单克隆形成率提高, 基因表达更接近原始态多能性特征。结果提示hESCs也存在两种多能性状态, 不同的体外培养环境可获得具备不同多能性特征的hESCs。原始态多能性状态的获得使hESCs在基因治疗、器官再生等领域具有广阔的应用前景, 而仅改变培养条件, 不依赖基因操作的培养方式大大提高了原始态多能性干细胞应用的安全性。
Abstract
Mouse embryonic stem cells possess two kinds of pluripotent states, naive pluripotent state and primed pluripotent state. The two cell types differ in colony morphology, self-renewal maintaining condition, gene expression, epigenetic features and single cell cloning efficiency. Human embryonic stem cells (hESCs) with the traditionally culture condition closer to the primed pluripotent state, and are difficult to achieve and maintain the naive pluripotent state without genetic modifications. Here we successfully converted the already established primed hESCs to naive hESCs with small chemical molecules under specific culture system. The converted hESCs showed domed-shaped colonies, had two activated X chromosomes and high single cell cloning efficiency, as well as molecular characteristics, and epigenetic feature was closer to the naive pluripotent state. The Results suggest that hESCs can possess different pluripotent characteristic without genetic modification when cultured under the specific conditions in vitro. The naive pluripotent hESCs has broad application prospects in developmental mechanism research and clinical applications such as gene therapy, organ regeneration. The cultivation method of small molecules without gene manipulation has greatly increased the security of naive pluripotent stem cell application.

欧阳琦, 杨青青, 周晓樱, 林戈, 卢光琇, 胡维新. 利用化学小分子实现人胚胎干细胞多能性状态的转化[J]. 激光生物学报, 2014, 23(4): 319. OUYANG Qi, YANG Qingqing, ZHOU Xiaoying, LIN Ge, LU Guangxiu, HU Weixin. Transformation from Primed to Naive Pluripotent State of Human Embryonic Stem cells by Small Chemical Molecules[J]. Acta Laser Biology Sinica, 2014, 23(4): 319.

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