细胞重编程将皮肤细胞转变为神经元

Two labs in China have independently succeeded in transforming skin cells into neurons using only a cocktail ¹ of chemicals, with one group using human cells from healthy individuals and Alzheimer's patients, and the other group using cells from mice. The two studies reinforce the idea that a purely ² chemical approach is a promising ³ way to scale up cell reprogramming research that may avoid the technical challenges and safety concerns associated with the more popular method of using transcription factors. Both papers appear on August 6 in the journal Cell Stem Cell. One of the challenges of forcing cells to change identity is that the cells you end up with may look normal but have different internal activities than their naturally forming counterparts. The two papers provide evidence that similar gene ⁴ expression, action potentials, and synapse ⁵ formation can be detected in transcription-factor-induced neurons as those generated from the chemical cocktails ⁶. (Both groups used mixtures of seven small molecules ⁷, but different recipes--outlined in detail in the supplemental information section of each paper--because they focused on different species.) , ,"We found that the conversion ⁸ process induced by our chemical strategy is accompanied by the down-regulation of [skin-cell] specific genes ⁹ and the increased expression of neuronal transcription factors," said human study co-author Jian Zhao, of the Shanghai Institutes for Biological Sciences and Tongji University. "By coordinating ¹⁰ multiple signaling pathways, these small molecules modulate ¹¹ neuronal transcription factor gene expression and thereby ¹² promote the neuronal cell transition." The authors add that the direct conversion bypasses a proliferative ¹³ intermediate progenitor ¹⁴ stage, which circumvents ¹⁵ safety issues posed by other reprogramming methods., ,Zhao's paper, co-led with cell biologist Gang Pei, also shows that the pure chemical protocol ¹⁶ can be used to make neurons from the skins cells of Alzheimer's patients. Most of the work using patient stem cells has been done by using transcription factors--molecules that affect which genes are expressed in a cell--to create induced pluripotent stem cells. Chemical cell reprogramming is seen as an alternative for disease modeling or even potential cell replacement ¹⁷ therapy of neurological disorders ¹⁸, but the "proof-of-concept" is still emerging.