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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）0 D' E3 y9 \1 ~* D% K
Human and mouse embryonic stem cells (ESCs) are derived from
+ M) L: y7 a$ O3 u6 ^4 F, jblastocyst-stage embryos but have very different biological properties,
# R4 ?& _6 |) l! K- `and molecular analyses suggest that the pluripotent state of
$ w# ?- G# X$ H6 x8 q# c7 @& Bhuman ESCs isolated so far corresponds to that of mouse-derived
+ ] \6 I$ _% [' T8 H% ?' Lepiblast stem cells (EpiSCs). Here we rewire the identity of conventional; F* t; c# |, T# a7 r) Z" \- j
human ESCs into a more immature state that extensively; x7 ~ y* n' y2 c0 _2 x0 v& @
shares defining features with pluripotent mouse ESCs. This was
9 G7 r; b7 i* @$ A5 ]achieved by ectopic induction of Oct4, Klf4, and Klf2 factors
t0 E* H$ g+ q1 z/ i. j% T) O2 ^combined with LIF and inhibitors of glycogen synthase kinase 3β6 E- N. S! b, v6 H8 a6 s# n U
(GSK3β) and mitogen-activated protein kinase (ERK1/2) pathway.: c2 `( z0 t8 x% z
Forskolin, a protein kinase A pathway agonist which can induce
% ?: U# A# Y9 n" N+ }- _: m; kKlf4 and Klf2 expression, transiently substitutes for the requirement( T' q; J8 Q, E. H! N4 ]0 J
for ectopic transgene expression. In contrast to conventional human
; [5 P8 Z- b4 LESCs, these epigenetically convertedcellshave growth properties,an. B4 g- P) `6 ?6 {/ B7 s0 R
X-chromosome activation state (XaXa), a gene expression profile, q4 t C" k/ g* _
and a signaling pathway dependence that are highly similar to those
( C, t7 S- C+ G* D* ]8 oof mouse ESCs. Finally, the same growth conditions allow the derivation8 R5 R( I8 A7 Z- \ a- L3 G
of human induced pluripotent stem (iPS) cells with similar1 f- w7 n; e# \7 ?) U2 e/ W
properties as mouse iPS cells. The generation of validated “naïve”
6 b2 l6 I3 W; l8 n# @human ESCs will allow the molecular dissection of a previously undefined
0 G, x/ y6 [% K! Vpluripotent state in humans and may open up new opportunities' A5 k& e9 d Q( @
for patient-specific, disease-relevant research.
' X/ @0 V- ]! y; m: p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
