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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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楼主
发表于 2011-9-19 23:19 |显示全部帖子 |倒序浏览 |打印
本帖最后由 naturalkillerce 于 2011-9-22 00:00 编辑
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! h+ ]$ m# W% `2 S+ V2 y, |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  R$ v+ R7 j% S; _) \) [& N

6 y% G4 Y: X- U$ V& l. f研究背景:5 R) j2 j: m5 ^, M
(1)干细胞能够分化为身体上不同细胞类型。就人而言,胚胎干细胞分化为三种细胞胚层---外胚层(ectoderm)、中胚层(mesoderm)和内胚层(endoderm)。但是人们仍然很难清晰地理解某些干细胞为何以及如何分化成特定胚层。不过,正是这些胚层发育为组织和器官。比如,内胚层分化形成胃、结肠和肺,中胚层分化形成血液、骨头和心脏组织,而外胚层则分化形成神经系统(脊椎、周围神经和大脑)、牙釉质、表皮、口腔黏膜、肛门、鼻孔、汗腺、头发和指甲。由此可知,人皮肤细胞与脑细胞、神经细胞相关,因为它们都是外胚层分化形成的。
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8 v2 y0 D3 F) E( g7 b, u; N' F(2)抑癌基因被人广泛地认为是一种当发生突变时将健康细胞变成癌性的肿瘤细胞。
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" ]9 G7 G7 Q$ a! G: {) ]; S: `/ t研究成果:) R* P4 a0 q, y- ^3 V
来自南加州大学凯克医学院、加州橘子郡儿童医院和纽约Good Samaritan医院医学中心的研究人员进行协同研究,成功地通过抑制p53---一个得到广泛研究的抑癌基因编码的一种蛋白---表达将人皮肤细胞转化为脑细胞,这意味着p53突变有助于确定细胞命运---不管是好的还是坏的---而不只是产生癌症的结果。! n0 B; p* J' k# B8 ]8 t5 K
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当抑制p53表达时,人皮肤细胞发展为看起来极其类似于人胚胎干细胞的细胞,但是不同于其他人造的多功能性干细胞---它们能分化为体内其他任何细胞,如诱导性多功能干细胞(induced pluripotent stem cells, iPSCs),因而它们很难控制---这些细胞只分化为来自同一胚层(即外胚层)的细胞。研究结果于2011年7月25日发表在American Association for the Advancement of Science (AAAS)网站上。  F, H' G: [& g: b7 D) w
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应用价值:
  A$ b) ~& z" f; x3 R! c2 `价值之一:当关闭抑癌基因p53时,人们就认为细胞变为癌性,该研究表明现实可能比人们所想的要复杂得多,细胞实际上只是变得更具可塑性,也可能发生好的结果。
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价值之二:阻断抑癌基因能把正常细胞变成干细胞样细胞,将为利用干细胞疗法更安全和更加实用治疗诸如多发性硬化症和癌症之类的疾病铺平道路。研究人员希望阻断其他胚层细胞的其他抑癌基因也有同样效果,若证实的话,也将会给干细胞疗法带来极大希望。

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4 V4 F! h, \9 K0 J6 U; K研究原文信息在16楼
4 ^# k8 a, M8 @' E研究原文在17楼
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发表于 2011-9-20 09:00 |显示全部帖子
回复 jingjing 的帖子
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谢谢指出错误之处,已经更改

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发表于 2011-9-20 13:21 |显示全部帖子
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. V9 K# ~4 H' p1 K相对于iPS,能分化为体内其他任何细胞,因而它们很难控制,是故用于治疗时风险性较大,我觉得这里还是有些区别的,因为抑制p53表达时,人皮肤细胞发展为看起来极其类似于人胚胎干细胞的细胞,只能分化为来自外胚层分化的细胞,即相对而言,细胞分化分化方向较明确一些,但是外胚层则分化形成神经系统(脊椎、周围神经和大脑)、牙釉质、表皮、口腔黏膜、肛门、鼻孔、汗腺、头发和指甲等等,细胞类型还是比较丰富的,如何实现精确和适量控制才是关键。
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发表于 2011-9-21 23:49 |显示全部帖子
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# U- L  f$ V2 n7 W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 |显示全部帖子
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4 m0 u4 v% h. C; |$ x, LScientists Grow Brain Cells from Skin: Cancer Cells and Stem Cells Share Same Origin, Research Shows" D' y% q  Q- q8 ~) [( l7 E! y* o

0 Z  w6 E6 D- o/ }4 yScienceDaily (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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, v# l5 ]2 T5 S% p"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.") T4 V" W) U+ m- I" i. ]! y
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." ]- i* s9 g9 G7 N  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.: g+ @0 m" a7 k+ \. J& u
"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."
% b5 u) ]. G! W) W/ G0 e+ 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.% R2 C4 L! y+ X( }2 F: I) i
When 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.
# ~3 W! P2 T* [0 {0 {"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."0 V6 ~$ B3 u* ^6 M6 ~, @5 S& P" R
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.
' p) B4 ]' f. [7 z% p1 O3 A% j+ EThis 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 |显示全部帖子
回复 naturalkillerce 的帖子- f& a; U8 w" }- p6 F. x. D

4 U3 c, {' d1 m  L* m) y该研究成果发表在PNAS上,论文信息为:  g+ \" _/ H/ T) L
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.11005091086 O( X. Q( H0 `( p1 N
http://www.pnas.org/content/108/31/12793

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发表于 2011-9-21 23:59 |显示全部帖子
回复 naturalkillerce 的帖子4 b4 I4 C- G* R; Z+ K% q

6 q- E/ j1 G- b# a7 y& v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 00:09 |显示全部帖子
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