新型人类基底状态天真多能干细胞的衍生
Ohad Gafni1, Leehee Weinberger1, Abed AlFatah Mansour1
11] The Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel [2].
Nature
|November 1, 2013
概括
研究人员已经成功地获得了人类的天真多能干细胞,反映了老鼠的天真干细胞. 这些细胞显示出再生医学和疾病建模的潜力.
科学领域:
- 干细胞生物学 干细胞生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 发育生物学 发展生物学
背景情况:
- 鼠标胚胎干细胞 (ES) 中的天真多能性是由白血病抑制因子 (LIF) 和2i/LIF条件维持的,其特征是特定的表观遗传标记和基因调节.
- 人类ES细胞表现出更接近化小鼠表皮质干细胞 (EpiSCs) 的表观遗传特征,这对建立天真多能性提出了挑战.
- 关键的差异包括OCT4增强剂的使用,X染色体无活化倾向,DNA甲基化水平和H3K27me3沉积在人类ES细胞中,与老鼠天真ES细胞相比.
研究的目的:
- 建立获得具有与小鼠原始ES细胞分子和功能等价性的人类原始多能干细胞的定义条件.
- 为了验证从原始化的人类ES细胞,体细胞 (通过iPSC) 和胚芽细胞中衍生出人类天真多能干细胞.
- 评估这些人类的天真多能细胞在跨物种的嵌合体形成和器官生成中的潜力.
主要方法:
- 在确定的条件下,从人类的天真多能干细胞衍生.
- 简单多能性的分子和表观遗传特征的表征.
- 通过与老鼠胚胎交叉物种的嵌合体生成来评估功能多能性.
主要成果:
- 成功地获得了基因未经修改的人类天真多能干细胞.
- 这些细胞表现出与老鼠天真ES细胞非常相似的分子特征,与原始化的人类多能细胞不同.
- 人类天真的iPS细胞表现出在产生跨物种化鼠胚胎的能力,这些胚胎经历了器官生成.
结论:
- 定义的条件使得人类天真多能干细胞的衍生成为可能,弥合了干细胞研究中的差距.
- 这些发现为再生医学,患者特异性疾病建模和研究早期人类发育提供了新的可能性.
- 化学胚胎的成功生成突显了人类原始干细胞的功能多能性和发育潜力.
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