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美国科学家证实阻断抑癌基因p53将人皮肤细胞转变为干细胞样细胞 [复制链接]

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发表于 2011-9-20 21:20 |只看该作者
希望对大家有用~
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发表于 2011-9-20 21:33 |只看该作者
回复 naturalkillerce 的帖子
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# R: b& o) n; l# M# D3 q我认为之所以抑制p53表达后皮肤细胞变得可塑就是因为将p53抑癌基因的检测和修复病变的功能给抑制了,然后就可以随意进行变化了,加上外界条件的刺激,再加上本身的已经导致的不稳定,所以这样就可以导致细胞类型的转变,当然,都是从外胚层分化来的细胞确实有可能有共同的特征,也可能在本质上有某种相似性,但是以抑制p53发生的转变,还是不能解释是因为这些细胞在母源上的相同从而能够发生分化的吧,09年有一篇文章说p53通路抑制iPS的形成,所以抑制p53会提高iPS的效率,恐怕这些是同样的机理吧~$ r6 A- k( T- s
但是这样其实真的不可避免的会产生cancer~所以临床应用还需谨慎啊。。。
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发表于 2011-9-21 23:41 |只看该作者
可不可以麻烦楼主将链接发上来小弟看一看,我刚找了也没找到!多谢了/ ~0 ^# }- b0 s% [

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发表于 2011-9-21 23:49 |只看该作者
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回复 开心果王 的帖子
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9 ]3 H1 U0 f" v3 o用Google找找很快的啦,输入关键词与,p53, ectoderm brain cell skin就可以了。

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发表于 2011-9-21 23:50 |只看该作者
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Scientists Grow Brain Cells from Skin: Cancer Cells and Stem Cells Share Same Origin, Research Shows9 f) `/ Y- M) U/ t  W: P& w, p

  v% J% j" Z9 o( y0 _# }ScienceDaily (July 19, 2011) — Oncogenes are generally thought to be genes that, when mutated, change healthy cells into cancerous tumor cells. Scientists at the Keck School of Medicine of the University of Southern California (USC) have proven that those genes also can change normal cells into stem-like cells, paving the way to a safer and more practical approach to treating diseases like multiple sclerosis and cancer with stem cell therapy.
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"The reality may be more complicated than people think," said Jiang F. Zhong, Ph.D., assistant professor of pathology at the Keck School. "What is a stem cell gene? What is a cancer gene? It may be the same thing."3 f2 k9 O' ~/ H2 s) q- G
Zhong and colleagues at the Children's Hospital of Orange County (CHOC) in California and Good Samaritan Hospital Medical Center in New York successfully converted human skin cells into brain cells by suppressing the expression of p53, a protein encoded by a widely studied oncogene. This suggests that p53 mutation helps determine cell fate -- good or bad -- rather than only the outcome of cancer.
2 F' X! a2 ]; e) M/ O0 l/ @The study is slated to appear in the online edition of Proceedings of the National Academy of Sciences, a peer-reviewed scientific journal, the week of July 18, 2011.
" B; \# N+ k: o1 K"When you turn off p53, people think the cell becomes cancerous because we tend to focus on the bad thing," Zhong said. "Actually, the cell becomes more plastic and could do good things, too. Let's say the cell is like a person who loses his job (the restriction of p53). He could become a criminal or he could find another job and have a positive effect on society. What pushes him one way or the other, we don't know because the environment is very complicated."
$ P, l/ |& J7 m. A2 M! k9 C" T% I. }( ]5 oStem cells can divide and differentiate into different types of cells in the body. In humans, embryonic stem cells differentiate into three families, or germ layers, of cells. The reasons why and how certain stem cells differentiate into particular layers are not clearly understood. However, from those layers, tissues and organs develop. The endoderm, for example, leads to formation of the stomach, colon and lungs, while the mesoderm forms blood, bone and heart tissue. In its study, Zhong's team examined human skin cells, which are related to brain and neural cells from the ectoderm.
9 ~* |* K8 {; ^6 Z6 a$ Z; kWhen p53 was suppressed, the skin cells developed into cells that looked exactly like human embryonic stem cells. But, unlike other human-made stem cells that are "pluripotent" and can become any other cells in the body, these cells differentiated only into cells from the same germ layer, ectoderm.
' ?5 M* X  a9 s' L: t"IPSCs [induced pluripotent stem cells] can turn into anything, so they are hard to control," Zhong said. "Our cells are staying within the ectoderm lineage."% J& F/ O( X2 z8 I" s/ M, G
Zhong said he expects that suppressing other oncogenes in other families of cells would have the same effect, which could have critical significance for stem cell therapy. Future research should focus on determining which genes to manipulate, Zhong said.
. N- ^3 _1 Q! g2 h8 j! ~; UThis study was supported by the CHOC Children's Foundation, CHOC Neuroscience Institute, Austin Ford Tribute Fund, W. M. Keck Foundation, National Institutes of Health and National Science Foundation.

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发表于 2011-9-21 23:56 |只看该作者
回复 naturalkillerce 的帖子
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该研究成果发表在PNAS上,论文信息为:6 y) x4 P* E; X6 B
Shengwen Calvin Li, Yangsun Jin, William G. Loudon, Yahui Song, Zhiwei Ma, Leslie P. Weiner, Jiang F. Zhong. Increase developmental plasticity of human keratinocytes with gene suppression. Proceedings of the National Academy of Sciences, 2011; DOI: 10.1073/pnas.1100509108: j$ _4 N+ k  y4 P0 G0 K
http://www.pnas.org/content/108/31/12793

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发表于 2011-9-21 23:59 |只看该作者
回复 naturalkillerce 的帖子
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! t3 M9 s8 [8 y3 S虽然在PNAS官网上不能下载,但在Google找到了原始文献,上传给大家分享一下:
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发表于 2011-9-22 00:04 |只看该作者
本帖最后由 懵懂干细胞 于 2011-9-22 00:05 编辑 % v+ e8 q$ J2 k' J" p) L

4 {) h8 n" d: l, f4 ]* h1、 1979年,6个科研小组同时发现了p53蛋白,p53基因;
8 j7 f; h/ k  D8 Z. X; j2、1980s中期,p53被普遍认为是个致癌基因,证据主要有两个:即外源p53基因的引入将正常细胞变成瘤细胞,另外就是瘤细胞中p53的异常高表达;+ n) U; s$ O; A7 ^# K' `' r) `/ x
3、1989年发现,p53是抑癌基因,以前用于论证p53是致癌基因的p53都是突变后的p53;6 t/ p* h5 n7 E& F& m
4、1992年p53基因敲除小鼠诞生,并发现缺陷p53的小鼠发育正常但非常容易患癌;% I. R  i0 }4 u6 s
5、2010年p53基因敲除大鼠诞生。
" ~6 C! K% ?. _% q' d我附上P53基因的一篇研究时间表吧!$ a! l" P( u4 L; Q
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* x, a2 g! d( o; v2 k7 x1 j9 F原文在17楼。
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