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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）
" {5 }/ F9 a7 J' p" d- P/ m/ B% KHuman and mouse embryonic stem cells (ESCs) are derived from
0 L0 q# }$ j$ c7 Qblastocyst-stage embryos but have very different biological properties,! P& i* _9 h0 s
and molecular analyses suggest that the pluripotent state of- Y2 l. U- z9 V2 |0 F* X
human ESCs isolated so far corresponds to that of mouse-derived" L% [$ t1 A) C( X
epiblast stem cells (EpiSCs). Here we rewire the identity of conventional
! F" b% l1 _. x1 V& d) y: ^human ESCs into a more immature state that extensively
% N% @: _* h5 nshares defining features with pluripotent mouse ESCs. This was
0 V. w) Y u& v& L: M' w' Wachieved by ectopic induction of Oct4, Klf4, and Klf2 factors
# z3 q7 K! L6 R& V) F5 D) q6 ]combined with LIF and inhibitors of glycogen synthase kinase 3β
; X I5 k( p' U7 A- ?) E3 w(GSK3β) and mitogen-activated protein kinase (ERK1/2) pathway.) p5 a1 b$ T" y ^$ D
Forskolin, a protein kinase A pathway agonist which can induce6 b! O9 Y! m7 y
Klf4 and Klf2 expression, transiently substitutes for the requirement
7 x: T' g, V2 F; x: D! F3 g0 N, Gfor ectopic transgene expression. In contrast to conventional human
7 d: [" C1 C0 D) b8 kESCs, these epigenetically convertedcellshave growth properties,an2 T* X9 R/ e( I+ X2 N0 c
X-chromosome activation state (XaXa), a gene expression profile,
+ S! ~- k; S5 s+ qand a signaling pathway dependence that are highly similar to those1 r% N% I1 y6 @
of mouse ESCs. Finally, the same growth conditions allow the derivation
5 H( X3 t; ]% q8 r5 \of human induced pluripotent stem (iPS) cells with similar8 ?7 O: i( a- u6 e# V( j& v1 q
properties as mouse iPS cells. The generation of validated “naïve”
' O& v5 S/ {" r& dhuman ESCs will allow the molecular dissection of a previously undefined
! E$ @8 m* d* k: Hpluripotent state in humans and may open up new opportunities, Y! K* ~2 W& l2 L
for patient-specific, disease-relevant research.
: j5 C' p% |, ?( c* g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
