相変わらず、周回遅れの当ブログですが、参考になればと思いRetraction Watch





This is such an extraordinary claim that a very high level of proof is required to sustain it and I do not think this level has been reached. I suspect that the results are artifacts derived from the following processes: (1) the tendency of cells with GFP reporters to go green as they are dying. (2) the ease of cross contamination of cell lines kept in the same lab.
I believe that the green transformation is indeed due to stress as reporters are often upregulated in stressed or dying cells. But the cells that go green may not be the ones in the later green colonies. I think these are more likely to be ES cells acquired by cross contamination and selected for growth by the B27-LlF medium.

The claim about all the other tissues being similarly reprogrammed by low pH treatment is truly extraordinary. Much more detail needs to be provided about the nature of the cells and the culture conditions. Otherwise this is simply not credible, since the principal cell type of several of these tissues is postmitotic.

STAP論文を説得させるためには、高いレベルの証拠が必要であり、今のSTAP論文ではこのレベルに達したとは思わない。 以下のartifactsな現象が懸念される。

私は、細胞が緑色に形質転換する現象は実際に細胞ストレスに起因すると考えています。しばしばストレスを受けた細胞や瀕死の細胞でアップレギュレーションされます。 しかし、緑色になる細胞は、後で緑色のコロニーになる細胞ではないかもしれません。


The DNA analysis of the chimeric mice is the only piece of data that does not fit with the contamination theory. But the DNA fragments in the chimeras don’t look the same as those in the lymphocytes. This assay is not properly explained. If it is just an agarose gel then the small bands could be anything. Moreover this figure has been reconstructed. It is normal practice to insert thin white lines between lanes taken from different gels (lanes 3 and 6 are spliced in). Also I find the leading edge of the GL band suspiciously sharp in #2-#5.
キメラマウスのDNA分析は、ES汚染では説明できない唯一のデータです。 しかし、キメラのDNA断片は、リンパ球のDNA断片と同じに見えません。 このアッセイは適切に説明されていません。 アガロースゲルで実験したなら、小さなバンドは何でもかまいません。 さらに、この図は作り直されています。 異なるゲルから取ったレーン間に細い白線を挿入するのが通常の方法です(レーン3とレーン6はスプライスインされます)。 また、#2-5でGLバンドの先端が疑惑を持たれるような鋭さとなっています。

Unfortunately, the paper presents only a superficial description of many critical aspects of the work. A detailed description of the methods used to induce and maintain SACs was not provided, and the mechanisms and explanations are either not compelling or poorly defined (Figure 3). Given the novelty of the claims, a thorough characterization of the SACs is warranted. as is some probing of the mechanisms. This would necessitate a more sophisticated genomic analysis of SACs, through microarray or RNA-seq, and genome-wide DNA methylation analysis — analyses that other pluripotent stem cell lines have been routinely subjected to and for which methods for smaller cell numbers have been developed.



1) From the experiments performed by the authors, it cannot be ruled out that rare multipotent progenitors are being selected for and expanded under stress conditions. While this in itself would be extremely interesting, it suggests a very concept [sic](*) than what is being claimed about reprogramming of “mature” adult somatic populations. It is unclear whether cells are harvested from any other stages than young (7-day old) mice. Might the cells in these young mice be errant migratory germ cells or some other stem cell-like progenitors? CD45+ cells are harvested from the spleens and these are called lymphocytes, but hematopoietic stem cells (HSCs) express CD45, and the spleen contains HSCs at this young age. Thus stress conditions may be acting on HSCs, rather than fully differentiated somatic cells, which would imply a very different main conclusion of this work. Should the authors wish to maintain their conclusion, they should rule out the potential germ cell or HSC origin of SACs. This could involve perhaps the examination of genomic imprints, or expression of c-Kit.

2) The analysis of TCRb gene rearrangement in fig S6 purporting to show derivation from fully mature T cells with TCRb rearrangement is flawed. If mice are clonally derived, they should have a single gene rearrangement, not a population of polyclonal rearrangements as appears in at least some of these animals. This analysis should be done using Southern Blots to avoid the problems of PCR contamination; see Hochedlinger and Jaenisch, Nature 2002.
注* 原文のまま《疑わしいまたは誤った原文をそのまま引用した際,引用語句の後に [sic] と記す》.


CD45 +細胞は脾臓から採取され、これらはリンパ球と呼ばれるが、造血幹細胞(HSC)はCD45を発現し、脾臓はこの若年時にHSCを含む。したがって、完全に分化した体細胞よりもストレス状態がHSCに作用した可能性があり、この場合は、本研究の結論と異なる。


マウスがクローン的に誘導される場合、それらは、これらの動物の少なくともいくつかに現れるようなポリクローナル転位の集団ではなく、単一の遺伝子再構成を有するべきである。この分析は、PCRコンタミネーションの問題を避けるためにサザンブロットで行う必要がある。 HochedlingerとJaenisch、Nature 2002を参照されたい。



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