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人类胚胎干细胞是朵奇葩精选

已有 11587 次阅读 2013-5-24 16:45 |个人分类:科研笔记|系统分类:论文交流| 干细胞, 奇葩

题记：人类是如此的聪慧和伟大，伟大到我们能改造生命；人类又是如此的微弱和渺小，渺小到我们还不能认识自己！

2007 年11月14日，《自然》杂志宣布，位于美国俄勒冈州比弗顿的国立灵长类动物研究中心科学家沙乌科莱特•米塔利波夫(Shoukhrat Mitalipov)率领的研究小组，成功克隆出猴胚胎，并从中获得两批胚胎干细胞，研究人员从克隆胚胎中已经培育出成熟的猴子心肌细胞和大脑神经细胞。

2013-5-15 该研究小组又在Cell在线发表论文称成功将人皮肤细胞转化成胚胎干细胞，可是这次他们却惹来了不少苦恼，难道沙乌科莱特•米塔利波夫是又一个黄禹锡（Woo Suk Hwang）？

Human Embryonic Stem Cells Derived by Somatic Cell Nuclear Transfer

Available online 15 May2013, Cell. http://dx.doi.org/10.1016/j.cell.2013.05.006

http://www.cell.com/fulltext/S0092-8674(13)00571-0

一周后，因被读者指控“图片重复使用”而正在接受《细胞》杂志的调查

http://pubpeer.com/publications/23683578

This paper reports thenovel creation of human embryonic stem cells from somatic nuclei. It hasreceived massive media coverage and is surely pencilled in as a strongcandidate for scientific publication of the year.

It does however haveseveral examples of image reuse which might be of interest to PubPeer membersand readers.

Fig. 2F NT-ESC colonywith typical morphology derived from a caffeine-treated SCNT human blastocyst.

Fig. 6D pluripotency markers (top left)

Fig. 6D pluripotency markers (top right)

Fig. s5, Expression of Pluripotency Markers in Human NT-ESCs and in Control IVF-ESCs Detected by Immunocytochemistry(top right)

Figure S6 MicroarrayScatterplot Analysis of Biological Replications within Each Cell Type(topcentre and top right are the same image)

- Fig. 2F is a slightlycropped version of the cell microscopy image in Fig. 6D top left.

- Fig. 6D top right, thecell microscopy image is a slightly cropped version of supplementary Fig. s5,top right. The cells in 6D are labelled as "h-ESO-NT1 Ph" yet infigure s5 they are labelled to be "hESO-7". We understand the formerto inherit caffeine-treated somatic nuclei whereas the latter are original stemcells.

Under pressure toassemble the figures for rapid publication, one can understand making a cut andpaste figure assembly mistake. Nevertheless it should be noted that imagecropping does take extra work.

- Figure S6 top centreand top right are the same image.

- Figure S6 middle leftand lower right are reported to be biological replicates of microarrayexpression quantitation. In those cases however the narrow spread indicatesthat the data are extremely similar and are only understandable as technicalreplicates (where the same RNA sample is hybridised to two different arrays).It is useful to do technical replicates to control experimentalreproducibility, but biological replicates are more valuable when reportingresults. They are not the same thing and should not be conflated. (For therecord, we did check the microarray data deposited at Gene Expression Omnibus(GSE46397)).

Lastly we note that, inthe paper, it is recorded that the journal Cell accepted this paper just 4 daysafter submission. Perhaps, under the circumstances, the pre-publication peerreview had to be a little hasty? At least here at Pubpeer, while conductingpost publication review, we can take as long as necessary to make up for thatlost time.

PS：

韩国科学家黄禹锡Science上的两篇人胚胎干细胞造假论文(Science 2004, 303: 1669和Science 2005, 308: 1777)

1. Science 2004, 303: 1669

This article has been retracted

Published Online February12 2004, Science 12 March 2004: Vol.303 no. 5664 pp. 1669-1674 DOI: 10.1126/science.1094515

REPORT

Evidence of a PluripotentHuman Embryonic Stem Cell Line Derived from a Cloned Blastocyst

http://www.sciencemag.org/content/303/5664/1669.full

Fig. Expression ofcharacteristic cell surface markers inhuman SCNT ES cells. SCNT-hES-1 cells expressedcell surface markers

2. Science 2005, 308: 1777

This article has been retracted

Published Online May 192005, Science 17 June 2005: Vol. 308no. 5729 pp. 1777-1783

DOI:10.1126/science.1112286

REPORT

Patient-SpecificEmbryonic Stem Cells Derived from Human SCNT Blastocysts

http://www.sciencemag.org/content/308/5729/1777.full

Fig. hESC linesestablished from NT blastocysts using patient somatic cells (NT-hESCs) arepluripotent with normal karyotypes

3. Cell Stem Cell, Volume1, Issue 3, 13 September 2007-cover paper 和Science,Volume 315, Issue 5811, 26 January 2007-cover paper

2007年11月是一个令人感慨的岁月，黄禹锡被废掉500天之后，达利教授功成名就！哈佛大学兼Boston儿童医院Daley实验室乔治·达利(George Daley)教授从黄禹锡Sciene“造假”论文中获取灵感，当年发表在Cell Stem Cell上的一篇封面论文宣布：2004年，由韩国胚胎干细胞专家黄禹锡博士建立的人类疾病基因胚胎干细胞株，已被该研究团队确认，这些细胞株的建立方法是不含外源性基因污染的单性繁殖胚胎干细胞，很有可能是一项历史性的创举。同年他们还利用小鼠的未受精卵，产生所谓的孤雌生殖（parthenogenetic）胚胎干细胞，证明孤雌胚胎干细胞的组织相容性，并发表了Science封面论文。

1. 区分孤雌和体细胞克隆胚胎干细胞的方法

Recombination Signatures Distinguish Embryonic Stem Cells Derived by Parthenogenesis and Somatic Cell Nuclear Transfer

Cell Stem Cell, Volume 1,Issue 3, 346-352, 13 September 2007, doi:10.1016/j.stem.2007.07.001

http://www.cell.com/cell-stem-cell/abstract/S1934-5909(07)00067-7

Cell Stem Cell, 13September 2007

2. 小鼠组织相容性孤雌生殖胚胎干细胞

Published Online December14 2006

Science 26 January 2007:

Vol. 315 no. 5811 pp.482-486 DOI: 10.1126/science.1133542

http://www.sciencemag.org/content/315/5811/482.abstract

RESEARCH ARTICLE

Histocompatible EmbryonicStem Cells by Parthenogenesis

Science, 26 January 2007

后记：

人类胚胎干细胞（引自百度百科http://baike.baidu.com/view/7042355.htm）

胚胎干细胞拥有类似胚胎的全能分化性，可以从单个的受精卵发育成完整的个体，能够给我们解释完整的发育体系，而成体个体来源的多能干细胞就不可能。同时，极早期的胚胎发育均可追溯到ES细胞，而不可能是成熟个体来源的多能干细胞。ES细胞也是唯一不死的细胞，能够非限定地分化，是细胞的源头。ES细胞天生就是全能的，这就是问题的关键，换言之，他们能制造机体需要的全部细胞。最后，ES细胞是遗传操作的最早期细胞。因此，尽管目前的争论集中在治疗方面，但也许ES细胞最伟大的用途是作为科学研究的工具。

人胚胎干细胞的分离及体外培养的成功，将给人类带来医学革命。如果科学家最终能够成功诱导和调控体外培养的胚胎干细胞正常的分化，这一技术将对基础研究和临床应用产生巨大的影响，有可能在以下领域发挥作用：体外研究人胚胎的发生发育，非正常发育（通过改变细胞系的靶基因），新人类基因的发现，药物筛选和致畸实验，以及作为组织移植、细胞治疗和基因治疗的细胞源等。

人胚胎干细胞提供了在细胞和分子水平上研究人体发育过程中的极早期事件的良好材料和方法，这种研究不会引起与胚胎实验相关的伦理问题。采用基因芯片等技术，比较胚胎干细胞以及不同发育阶段的干细胞和分化细胞的基因转录和表达，可以确定胚胎发育及细胞分化的分子机制，发现新的人类基因。结合基因打靶技术，可发现不同基因在生命活动中的功能等。另一个令人兴奋的应用在于新药的发现及筛选。胚胎干细胞提供了新药的药理、药效、毒理及药代等研究的细胞水平的研究手段，大大减少了药物实验所需动物的数量。目前上述实验使用的细胞系或来自其他种属的细胞系，很多时候并不能真正代表正常的人体细胞对药物的反应。胚胎干细胞还可用来研究人类疾病的发生机制和发展过程，以便找到有效和持久的治疗方法。