Artificial acceleration of mammalian cell reprogramming by bacterial proteins
Artificial acceleration of mammalian cell reprogramming by bacterial proteins
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DOI：
10.1111/gtc.12519
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发表时间：
2017-10
期刊：
影响因子：
2.1
通讯作者：
Takashi Ikeda;I. Uchiyama;Mio Iwasaki;Tetsuhiko Sasaki;M. Nakagawa;K. Okita;S. Masui
中科院分区：
文献类型：
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作者：
Takashi Ikeda;I. Uchiyama;Mio Iwasaki;Tetsuhiko Sasaki;M. Nakagawa;K. Okita;S. Masui
细胞重编程和分化的分子机制涉及多种信号传导因子。已发现小分子化合物可通过细胞蛋白质相互作用来人为地影响这些因素。尽管此类小分子化合物可用于增强重编程和分化并显示这些事件背后的机制，但筛选通常需要大量化合物才能仅识别极少量的命中（例如，数万种化合物中的一个命中）。在这里，我们展示了异种特异性基因产物可以影响细胞重编程为多能性的效率的概念证明。 30 个特定于 Wolbachia pipientis 细菌的基因与能够在哺乳动物细胞中产生诱导多能干细胞的重编程因子（Oct4、Sox2、Klf4 和 c-Myc）一起被单独强制表达，其中 8 个被发现对重编程效率产生正向或负向影响（命中率 26.7%）。机制分析表明其中一种蛋白质与细胞骨架相互作用以促进重编程。我们的结果提出了异种特异性基因产物为研究细胞身份调节机制提供另一种方法的可能性。
The molecular mechanisms of cell reprogramming and differentiation involve various signaling factors. Small molecule compounds have been identified to artificially influence these factors through interacting cellular proteins. Although such small molecule compounds are useful to enhance reprogramming and differentiation and to show the mechanisms that underlie these events, the screening usually requires a large number of compounds to identify only a very small number of hits (e.g., one hit among several tens of thousands of compounds). Here, we show a proof of concept that xenospecific gene products can affect the efficiency of cell reprogramming to pluripotency. Thirty genes specific for the bacterium Wolbachia pipientis were forcibly expressed individually along with reprogramming factors (Oct4, Sox2, Klf4 and c‐Myc) that can generate induced pluripotent stem cells in mammalian cells, and eight were found to affect the reprogramming efficiency either positively or negatively (hit rate 26.7%). Mechanistic analysis suggested one of these proteins interacted with cytoskeleton to promote reprogramming. Our results raise the possibility that xenospecific gene products provide an alternative way to study the regulatory mechanism of cell identity.