摘要：一个突破性的研究：通过重新编码处理，人体表皮细胞直接转化成大脑细胞，中间过程不经过干细胞状态。研究技术出奇的简单——激活表皮细胞的3个基因，在胚胎期大脑发育过程中，这3个基因是活跃表达的。
成纤维细胞的光学显微图
瑞典隆德大学（ Lund University）的研究小组首次成功地把人类表皮细胞转化成特定类型的神经细胞。通过重新编码技术实现结缔组织细胞（成纤维细胞）向成神经细胞直接转化，器官移植研究将进入下一阶段的新领域。这一发现改变关于分化细胞功能和潜能的根本看法，同时用分化细胞取代干细胞作为发育起点，可以避免在胚胎干细胞研究方面引起的伦理争议。
该研究小组负责人Malin Parmar对成纤维细胞如此“乐意”地接受再分化指令表示吃惊。
Malin Parma说：“起初只是出于兴趣去尝试，也不认为能成功，然而我们很快就发现，成纤维细胞令人吃惊地接受了分化指令。”这一研究还表明，表皮细胞可直接转化成神经细胞的一些特定类型。相关论文发表在最新Proceedings of the National Academy of Sciences期刊上。
通过活化另外2个基因表达，研究人员在试验过程中获得能分泌多巴胺的脑细胞，这类脑细胞在帕金森疾病中是凋亡的，因此，研究结果是朝着诱导的神经细胞在医学应用方向迈出的重要一步。这类细胞也可以作为研究各类神经衰退功能的疾病模型。
旧的重新编码方法——表皮细胞要经历转化成多能干细胞的中间过程，此类干细胞成为诱导干细胞。而新的重新编码方法可以实现由表皮细胞直接转化成神经细胞，中间不经历干细胞阶段。组织器官移植时， 不经历干细胞阶段意味着降低了移植器官癌化的风险。长期以来，阻碍干细胞研究的障碍是：移植器官中特定的干细胞会不断地分裂，最后导致形成癌细胞。
直接分化技术在应用于临床治疗之前，要更多地研究新转化细胞如何在大脑中存活和执行生理功能。我们希望医生能够把患者皮肤分化成脑细胞用于移植，这是美好的憧憬。此外，与外源供体组织相比，患者自身定向诱导的细胞组织能够更好地被机体免疫系统接纳。
Malin Parmar将继续使用这一新技术分化更多类型的脑细胞，我们希望能够分化分泌多巴胺的脑细胞，治疗帕金森疾病。长远来看，这绝对是一个好主意。(生物探索译 Pobee)
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生物探索推荐英文
New Genetic Technique Converts Skin Cells Into Brain Cells
A research breakthrough has proven that it is possible to reprogram mature cells from human skin directly into brain cells, without passing through the stem cell stage. The unexpectedly simple technique involves activating three genes in the skin cells; genes which are already known to be active in the formation of brain cells at the fetal stage.
For the first time, a research group at Lund University in Sweden has succeeded in creating specific types of nerve cells from human skin. By reprogramming connective tissue cells, called fibroblasts, directly into nerve cells, a new field has been opened up with the potential to take research on cell transplants to the next level. The discovery represents a fundamental change in the view of the function and capacity of mature cells. By taking mature cells as their starting point instead of stem cells, the Lund researchers also avoid the ethical issues linked to research on embryonic stem cells.
Head of the research group Malin Parmar was surprised at how receptive the fibroblasts were to new instructions.
"We didn't really believe this would work, to begin with it was mostly just an interesting experiment to try. However, we soon saw that the cells were surprisingly receptive to instructions." The study, which was published in the latest issue of the Proceedings of the National Academy of Sciences, also shows that the skin cells can be directed to become certain types of nerve cells.
In experiments where a further two genes were activated, the researchers have been able to produce dopamine brain cells, the type of cell which dies in Parkinson's disease. The research findings are therefore an important step towards the goal of producing nerve cells for transplant which originate from the patients themselves. The cells could also be used as disease models in research on various neurodegenerative diseases.
Unlike older reprogramming methods, where skin cells are turned into pluripotent stem cells, known as IPS cells, direct reprogramming means that the skin cells do not pass through the stem cell stage when they are converted into nerve cells. Skipping the stem cell stage probably eliminates the risk of tumours forming when the cells are transplanted. Stem cell research has long been hampered by the propensity of certain stem cells to continue to divide and form tumours after being transplanted.
Before the direct conversion technique can be used in clinical practice, more research is needed on how the new nerve cells survive and function in the brain. The vision for the future is that doctors will be able to produce the brain cells that a patient needs from a simple skin or hair sample. In addition, it is presumed that specifically designed cells originating from the patient would be accepted better by the body's immune system than transplanted cells from donor tissue.
"This is the big idea in the long run. We hope to be able to do a biopsy on a patient, make dopamine cells, for example, and then transplant them as a treatment for Parkinson's disease," says Malin Parmar, who is now continuing the research to develop more types of brain cells using the new technique.
