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南方科技大学公共卫生及应急管理学院2026级博士研究生招生报考通知（长期有效）

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[资源] 人类胚胎干细胞经表观修饰后生物学特性可与小鼠胚胎干细胞相似

Human embryonic stem cells with biological and epigenetic characteristics similar to those of mouse ESCs
人类胚胎干细胞经表观修饰后生物学特性可与小鼠胚胎干细胞相似
Rudolf Jaenisch
2010 PNAS
Abstract：Human and mouse embryonic stem cells (ESCs) are derived fromblastocyst-stage embryos but have very different biological properies, and molecular analyses suggest that the pluripotent state ofhuman ESCs isolated so far corresponds to that of mousederivedepiblast stem cells (EpiSCs). Here we rewire the identity of conventional human ESCs into a more immature state that extensivelyshares defining features with pluripotent mouse ESCs. This wasachieved by ectopic induction of Oct4, Klf4, and Klf2 factorscombined with LIF and inhibitors of glycogen synthase kinase 3β(GSK3β) and mitogen-activated protein kinase (ERK1/2) pathway.Forskolin, a protein kinase Apathway agonist which can induceKlf4 and Klf2 expression, transiently substitutes for the requirementfor ectopic transgene expression. In contrast to conventional humanESCs, these epigenetically convertedcellshavegrowthproperties, anX-chromosome activation state (XaXa), a gene expression profile,and a signaling pathway dependence that are highly similar to thoseof mouse ESCs. Finally, the same growth conditions allow the deri-vation of human induced pluripotent stem (iPS) cells with similarproperties as mouse iPS cells. The generation of validated “naïve”human ESCs will allow the molecular dissection of a previously undefined pluripotent state in humans and may open up new oppor-tunities for patient-specific, disease-relevant research.
摘要：•人类和小鼠的胚胎干细胞（h/mESCs）来源于胚泡时期胚胎，研究显示，二者的细胞分化潜能并不相同。相关分析表明，人类ESCs的分化潜能仅与小鼠外胚层干细胞（EpiSCs）相似。本研究通过向hESCs中导入Oct4, Klf4和Klf2 因子，LIF、GSK3β抑制因子及ERK1/2。为了诱导Klf4和Klf2的表达，我们将其诱导剂毛猴素也一同转染入hESCs。与传统的hESCs相比，这种经过后天修饰的细胞具有生长潜能，具有X染色体激活区；利用基因芯片技术分析该种细胞的基因表达，发现与mESCs中基因表达相似。最后，相同的培养条件能同时诱导出人类诱导式多能性干细胞（hiPS）和miPS。这种更具分化潜能的“原始”细胞，有利于我们深入了解人类干细胞的更多的分化潜能，并将其应用与疾病的基础研究与治疗。
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[ Last edited by silicare on 2011-5-23 at 17:50 ]

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