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刘实对丁盛等的此篇论文的科学批评经审查后已发表在《细胞-干细胞》杂志的网上，内容如下：
z s3 r) K" X7 R- ISome concerns about the protein-induced pluripotent stem cells (piPSCs)
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# @. T% u: z% \3 N& @$ HThis Brief Report has generated a huge interest that even resulted in a report in The Wall Street Journal. Ding’s protein-induced pluripotent stem cells (piPSCs) was described as “safer iPSCs” because the chemical reprogramming “effectively eliminates any risk of modifying the target cell genome by exogenous genetic sequences, which are associated with all previous iPSC methods”. 0 C7 S/ [0 q# w; H" Y& J
However, this statement may just be one of another hype which have been coming up and then going away in the hot but unstable iPSC research field.
) x4 B& x y; u1 C: s" ? From the perspective of Central Dogma, the genetic risk of exogenous genes may well be realized with their transcription into some mRNAs and then translation into some proteins. Thus, merely avoiding the upstream oncogenes but nevertheless employing the downstream oncoproteins would not logically eliminate the risk on the end point of the same line of genetic-chemical flow. 0 }8 U7 n4 m4 e: d; B. ]- E
From the observations on genetically engineered iPSCs (giPSCs), it appeared that the permanent presence of exogenes is not even required for generation of giPSCs. What needed might well be a temporary boost of some proteins from some oncogenes (which are endogenously present but exogenously enhanced) to activate the cell reproduction from a dormant/quiescent state into a hyperactive/“immortal” state. Thus, direct shortening of the same activation circuit with a near entry would not change the underlying “reprogramming”/oncogenesis process. 4 n9 j5 ?- J. ~# I
From the actual data presented by this piPSC report, it is clear that some epigenetic changes happened in the nuclear genomes of the cells being “induced”. No matter how “similar” the iPSC researchers would claim for the comparison between these piPSCs and ESCs, these changes would still distinct these piPSCs from ESCs, just as the giPSCs now become distinct from ESCs after the “indistinguishable” claim is broken. & e/ w% H) E0 a( Q+ @7 X2 b0 |
So, what is the evidence for the “safer” iPSCs? There is NONE in this report. 2 E* A5 ?# ~! O1 j5 D7 j
However, there are already some unsafe indications for these piPSCs. - ~6 O# }- G6 a+ `# L, Y' ~8 |
For example, these piPSCs were shown to form three germ layer cells including neural progenitor cells and characteristic neurons, satisfying the malignant tumor definition for teratomas as recently stated by a group of top iPS researchers. ( }, Y2 x5 ^: [( a; z
Another unsafe nature of the piPSCs is their potential to pass incorrectly programmed information to the offspring because the claimed “germline contribution” However, after carefully uating their data, I am not even convinced to accept the conclusion of germline contribution from these piPSCs. The detection of some GFP reporters in the cell-mixed tissue from gonad does not necessarily mean that these GFP reporters are derived from pure germline cells. In addition, germline cells (capable of passing genetic information to the next generation) should not be confused with germ layers (primary tissues responsible for organogenesis of the same individual in the current generation).
* f2 \8 Q$ m s; q7 `5 r" u Thus, it appears to me that, as the “induction” of pluripotent stem cells even becomes a routine job for some chemists, more and more “relaxed” use of biological terms becomes a reality. But these incorrect usages of some strict biological terms would not enrich our knowledge on the chemistry of life but only add to the already confused iPSC/stem cell research field. ! W9 ~3 I7 }: w5 B5 I, s8 c
By the way, I found the composite images of PCR analyses “unprofessional” because the bands in some “lanes” are not even vertically aligned. I also found it uneasy to see the missing disclosure of an important conflict of interest – a founder role of Dr. Ding in Stemgent which is selling many iPS products. I wish these data and acknowledgement problems could be addressed in the response to this Letter along with the answers to my scientific questions described earlier. 7 g9 f# i2 E z* Y
(Complete comment can be read free of charge in Logical Biology 9: 16-18, 2009 at http://im1.biz) |
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发表于 2009-5-12 10:27
发表于 2009-6-11 21:40
