人干细胞多潜能态基态研究新突破－Human embryonic stem cells with biological and

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摘要与摘要翻译（翻译水平不太好，大家感兴趣还是看看这篇文章）（文章附后）6 M" F, {* d: r0 g) W
Human and mouse embryonic stem cells (ESCs) are derived from4 S8 U( \. ^6 D
blastocyst-stage embryos but have very different biological properties,2 U5 L- C9 |3 I1 K
and molecular analyses suggest that the pluripotent state of
$ P/ f# `- s6 ^# N7 ]3 k) v0 V4 whuman ESCs isolated so far corresponds to that of mouse-derived; [/ Y) F1 J8 k6 g) D
epiblast stem cells (EpiSCs). Here we rewire the identity of conventional" T& t5 n! ]1 S3 D: s
human ESCs into a more immature state that extensively: }3 Y; f" m- a6 V' c
shares defining features with pluripotent mouse ESCs. This was1 t- B8 r1 X2 w# c3 T. L
achieved by ectopic induction of Oct4, Klf4, and Klf2 factors3 V/ a: \3 A* p* [5 X# b( N
combined with LIF and inhibitors of glycogen synthase kinase 3β
; v, N8 @: M2 }7 s! _1 S7 |(GSK3β) and mitogen-activated protein kinase (ERK1/2) pathway.
  z1 z) y# N% @' T. A: B& ~Forskolin, a protein kinase A pathway agonist which can induce
  v! _- V; c& H$ ]7 p1 eKlf4 and Klf2 expression, transiently substitutes for the requirement
* T8 H) e4 Z" r3 L+ P! [for ectopic transgene expression. In contrast to conventional human- Z& h& {8 j) m* y6 j
ESCs, these epigenetically convertedcellshave growth properties,an) ?/ [- [5 ~8 Z3 C4 G5 t1 B
X-chromosome activation state (XaXa), a gene expression profile,7 V& A* w2 `7 {. y( `
and a signaling pathway dependence that are highly similar to those  w4 F8 A) Q  [5 D) }
of mouse ESCs. Finally, the same growth conditions allow the derivation- b3 L) G- e# X2 `4 o4 c+ P
of human induced pluripotent stem (iPS) cells with similar
( C: g" `$ Y5 d2 B7 Mproperties as mouse iPS cells. The generation of validated “naïve”
3 M7 }" }1 o! l1 nhuman ESCs will allow the molecular dissection of a previously undefined: E& \  U; C6 M1 u8 _5 E% o
pluripotent state in humans and may open up new opportunities  x1 F: ~7 j! q
for patient-specific, disease-relevant research.# h4 m* N9 x2 V, k
人和鼠的胚胎干细胞ESC都是来自于胚胎胚泡期的细胞，但它们的生物学特性存在很大差异，而且分子水平研究表明分离的人胚胎干细胞ESC与小鼠的外胚层干细胞(EpiSCs)有相当的多潜能能态。我们的研究表明，人的ESC细胞可以转变到一种更不成熟状态，在这种状态下，人的ESC细胞广泛地呈现小鼠ESC细胞的特征。这一研究通过表达Oct4,Klf2和Klf4因子并联合使用LIF及GSK3β、ERK1/2抑制剂(PD/CH)而实现。Forskolin(血小板凝集抑制剂)，一种蛋白激酶A信号通路的激活剂，它能够诱导Klf2和Klf4因子表达,瞬间替代相应转基因的表达。与传统的人ESC细胞相比，这些表观遗传改变的ESC细胞与小鼠ESC细胞高度相似：生长特性、一条X染色体被激活（XaXi→XaXa）、基因转录集、信号通路。最后，在相同的培养条件下，证实人源iPS细胞与小鼠源iPS细胞具相似特性。人“基态“ESC细胞的产生将有助于从分子水平分析人ESC细胞先前未定义的多潜能状态，也为患者特异性和疾病相关性研究开辟新途径。

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