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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）
% ~# b# P- l( ]: U- rHuman and mouse embryonic stem cells (ESCs) are derived from
3 y1 E; p p+ C* S# kblastocyst-stage embryos but have very different biological properties,
' e& m, m" x( i+ Q5 Tand molecular analyses suggest that the pluripotent state of
' K$ j; h$ a. V5 s1 mhuman ESCs isolated so far corresponds to that of mouse-derived
* o% k2 z- ^6 repiblast stem cells (EpiSCs). Here we rewire the identity of conventional! {0 |* S* e- H6 S- e, ?- X; L
human ESCs into a more immature state that extensively
; p; V5 n; `; o$ p5 h L: dshares defining features with pluripotent mouse ESCs. This was
9 u- r& Y! B. c+ ^( l& Xachieved by ectopic induction of Oct4, Klf4, and Klf2 factors, U8 V! g) N* S; L! ^: o
combined with LIF and inhibitors of glycogen synthase kinase 3β1 _+ ^8 S8 m% M* d, ^
(GSK3β) and mitogen-activated protein kinase (ERK1/2) pathway.
3 f: u- V4 ^) {; JForskolin, a protein kinase A pathway agonist which can induce
4 S1 g# F4 d9 e" w1 XKlf4 and Klf2 expression, transiently substitutes for the requirement6 r$ j& u, s5 C: Z$ S7 w) Z/ ]
for ectopic transgene expression. In contrast to conventional human' v! z5 G( h# q, q( b
ESCs, these epigenetically convertedcellshave growth properties,an# U. U* \) I, W5 E. @6 } \
X-chromosome activation state (XaXa), a gene expression profile,$ v; c% q+ r: ~0 J2 X. y& n
and a signaling pathway dependence that are highly similar to those, ^4 F$ t5 Y! Q0 Z9 A
of mouse ESCs. Finally, the same growth conditions allow the derivation
. M' G3 [& q; o# Rof human induced pluripotent stem (iPS) cells with similar
, u; O/ E- n" x5 R6 f. i1 gproperties as mouse iPS cells. The generation of validated “naïve”
! r3 g- |( r( t5 a0 z) z3 ohuman ESCs will allow the molecular dissection of a previously undefined: H1 c" d/ m8 W+ M( j) j
pluripotent state in humans and may open up new opportunities. g: [; W K ]7 J. S3 Z
for patient-specific, disease-relevant research.+ O3 d% ^8 {7 _4 n: X% C
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
