通常人们认为人的成熟细胞在自然环境中没有去分化成干细胞的能力，但哈佛大学的Jayara Rajagopal教授近期让人大吃一惊的发现：在受压力或者损伤的情况下，哺乳动物的普通成熟细胞可以去分化成全能性的干细胞。
三篇强有力的相关研究文章发表在这几周的Nature上面。来自日本Riken研究所和哈佛学者们报道了新生的小鼠脾脏细胞在“酸浴”(在培养皿中加入咖啡弱酸)的压力下发生了去分化，形成了干细胞。
不过“酸浴”实验的近期遭遇了空前的信任危机。日本的这个实验没有办法重复出来。Riken研究所的调查组发现该提出该方法的文章作者Haruko Obokata在试验中有两处造假，还有一个数据是完全捏造的。这极大的损伤了该文章的有效性，甚至有可能会导致文章被召回。
但是其他的三个类似实验，由不同的科研团队分别在哺乳动物胃，支气管，肾脏细胞中完成—并没有多少非议。其中有两项还在Faculty of 1000中被广泛讨论。
这三个研究是具有重大意义和令人充满想象空间的，宾夕法尼亚大学的发育免疫学家Avinash Bhandoola评论说。匹兹堡大学的癌症研究专家Michael Lotze在访谈中表示：“这三篇研究的潜力是非凡的，它们从更深层次揭示了细胞面对压力时的可塑性，同时为人类认识癌症提供了极大的启发。“
虽然很久以前成熟细胞已经被证明可以通过体外人工改造的方式形成具有分化潜力的干细胞iPSCs。但是从来没有试验能证实，成熟哺乳动物细胞在自然环境中也可以去分化成干细胞。至少上面三个实验已经证明了，在特定环境下，这一切是可能的。
这三个实验和”酸浴”实验其实是有很多关键性的区别的。首先，细胞的压力来源不同：这些实验都没用到酸性物质。其次，”酸浴”实验是在体外（in vitro）完成的，在细胞内植入了GFP报告基因的同时损伤了细胞，目的是只要细胞一表达象征分化潜力的Oct4基因，GFP就会点亮细胞。而另外这三个实验是在体内（in vivo）进行的,科学家损伤了细胞以后，通过谱系追踪技术lineage tracing techniques）来观察成熟细胞的去分化情况。（其中有2篇是观察损伤成熟细胞周边细胞的去分化情况，还有一篇既追踪了受损细胞又追踪了周边细胞的情况）。
第三点，其他三个实验仅仅报道了上皮细胞的去分化。而“酸浴”实验声称不同的组织都发现了去分化的现象。
最后，在其他三个实验中，细胞并没有像“酸浴”实验声称的那样胚胎化。成熟细胞反转成了一种具有可塑性的类似干细胞的中间形态，看起来像上皮组织面对干细胞损伤做出的自然反应。
其他方面也还有一些区别，但上述四点为最关键性的区别。
相关文章：
两个实验组研究：干细胞损伤引发的上皮细胞去分化过程
Dedifferentiation of committed epithelial cells into stem cells in vivo
Nature 503, 218–223 (14 November 2013) doi:10.1038/nature12777
Differentiated Troy+ chief cells act as reserve stem cells to generate all lineages of the stomach epithelium.
Cell. 2013 Oct 10;155(2):357-68. doi: 10.1016/j.cell.2013.09.008.
第三个实验组研究：应对肾上皮细胞损伤的去分化
Differentiated kidney epithelial cells repair injured proximal tubule.
Proc Natl Acad Sci U S A. 2014 Jan 28;111(4):1527-32. doi: 10.1073/pnas.1310653110. Epub 2013 Oct 14.
英文版：
May Stress Naturally Turn Mature Cells Into Stem Cells?
Usually people think that people mature cells in their natural environment did not go the ability to differentiate into stem cells, but Jayara Rajagopal professor at Harvard University, recently found a surprise: in the case under pressure or injury mammals ordinary mature cells can go differentiate into totipotent stem cells.
Three strong research published in this weeks issue of Nature above. From Japan Riken Institute and Harvard scholars reported that newborn mouse spleen cells in the "acid bath" (coffee weak acid is added in a dish) pressure dedifferentiation, forming stem cells.
But "acid bath" experiment recently suffered an unprecedented crisis of confidence. Japan is no way to duplicate this experiment out. Riken Institute, the investigation team found that the proposed method of the authors, there are two Haruko Obokata fraud, there is a completely fabricated data in the test. This greatly damage the effectiveness of the article, may even result in the article being recalled.
But the other three similar experiments in mammalian stomach, bronchus, kidney cells, carried out by different research teams, respectively - and not much criticism. Two of these are still Faculty of 1000 is widely discussed.
These three studies are of great significance and it is full of imagination, development immunologist at the University of Pennsylvania Avinash Bhandoola commented. University of Pittsburgh Cancer researcher Michael Lotze said in an interview: "The potential of these three studies are extraordinary, they reveal the plasticity of the cells in the face of pressure from a deeper level, while providing a great inspiration for the human understanding cancer. "
Although long ago mature cells have been shown to have formed iPSCs differentiation potential of stem cells in vitro engineered by the way. But never test can confirm, mature mammalian cells in their natural environment can go differentiate into stem cells. At least three experiments have demonstrated above, under certain circumstances, all of this is possible.
The three experiments and "acid bath" experiments are in fact many critical differences. First, pressure-derived cells are different: these experiments did not use acidic substances. Secondly, the "acid bath" experiments in vitro (in vitro) to complete, in the implanted cells while the damage to the reporter gene GFP cells, as long as the purpose of the cell is a symbolic expression of the differentiation potential of Oct4 gene, GFP will light cells. While the other three experiments in vivo (in vivo) carried out, scientists damaged cells after lineage tracking through (Lineage tracing techniques) to observe to the differentiation of mature cells. (Of which two are to observe the differentiation of mature cells damage the surrounding cells, as well as an already damaged cells tracked and traced the circumstances surrounding the cells).
Third, the other three experiments just reported to the epithelial cell differentiation. The "acid bath" experiment claiming different organizations have found the phenomenon of dedifferentiation.
Finally, in the other three experiments, the cells did not like the "acid bath" experiment claims to be the embryo of. Become a mature cell reversal intermediate form similar malleable stem cells that looks like the face of a natural response to epithelial tissue stem cell damage made.
There are also a number of other differences, but the four most critical point of difference.
Related articles:
Two experimental groups study: Stem cell damage caused by epithelial dedifferentiation
Dedifferentiation of committed epithelial cells into stem cells in vivo
Nature 503, 218–223 (14 November 2013) doi:10.1038/nature12777
Differentiated Troy+ chief cells act as reserve stem cells to generate all lineages of the stomach epithelium.
Cell. 2013 Oct 10;155(2):357-68. doi: 10.1016/j.cell.2013.09.008.
A third study of experimental groups: Responding kidney epithelial cell injury dedifferentiation
Differentiated kidney epithelial cells repair injured proximal tubule.
Proc Natl Acad Sci U S A. 2014 Jan 28;111(4):1527-32. doi: 10.1073/pnas.1310653110. Epub 2013 Oct 14.
