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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）
) k/ {3 M* L5 `: fHuman and mouse embryonic stem cells (ESCs) are derived from
0 J& @% ?1 e8 y2 @$ [6 F8 h( wblastocyst-stage embryos but have very different biological properties," T* f/ T- R5 k7 ?; X
and molecular analyses suggest that the pluripotent state of
8 k2 A2 e* x, E/ m% l# Fhuman ESCs isolated so far corresponds to that of mouse-derived
4 X& [- @8 B7 Z2 Y' C( f$ Yepiblast stem cells (EpiSCs). Here we rewire the identity of conventional- @* O: G8 E. \7 V8 x5 z
human ESCs into a more immature state that extensively, v/ r+ X7 r; g* O# z( v8 I+ R
shares defining features with pluripotent mouse ESCs. This was' y3 C$ f! m# D2 W
achieved by ectopic induction of Oct4, Klf4, and Klf2 factors- L4 F5 M* O& W. }. I- q- E
combined with LIF and inhibitors of glycogen synthase kinase 3β
+ j1 W; t. n C# D& R) `8 ~(GSK3β) and mitogen-activated protein kinase (ERK1/2) pathway.% ~ j5 w' k* |
Forskolin, a protein kinase A pathway agonist which can induce
' ~7 |- I; N$ h8 n IKlf4 and Klf2 expression, transiently substitutes for the requirement
9 \! W% Q, ]% G! j1 j5 Y8 }5 d, }for ectopic transgene expression. In contrast to conventional human5 m" I+ p/ p9 b
ESCs, these epigenetically convertedcellshave growth properties,an# v6 A- k- y, a+ W4 n" o
X-chromosome activation state (XaXa), a gene expression profile,/ z9 v5 i% W# q- C( M" J
and a signaling pathway dependence that are highly similar to those" {8 e4 i1 U5 |$ C- N
of mouse ESCs. Finally, the same growth conditions allow the derivation, g( f5 }" Q1 c( C( o9 }
of human induced pluripotent stem (iPS) cells with similar+ l4 b$ T. D! ^- u
properties as mouse iPS cells. The generation of validated “naïve”$ ^( a4 B. D4 m% c+ }) e: l
human ESCs will allow the molecular dissection of a previously undefined
H5 z$ V3 E: X9 F+ R3 U; Gpluripotent state in humans and may open up new opportunities
% v2 X2 P$ p/ Efor patient-specific, disease-relevant research.$ D! U/ c3 H% d& w# Y4 z
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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发表于 2010-5-9 22:47
发表于 2010-5-10 18:33
