All-optical regulation of gene expression in targeted cells.

All-optical regulation of gene expression in targeted cells.
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靶细胞基因表达的全光调控

DOI:
10.1038/srep05346
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发表时间:
2014-06-18
期刊:
影响因子:
4.6
通讯作者:
Wang C
Wang C
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Wang Y;He H;Li S;Liu D;Lan B;Hu M;Cao Y;Wang C

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基因的可控表达一直是生物医学研究和临床应用的一个挑战和重要意义。最近,已经开发了基于额外工程化光敏蛋白的各种方法来提供用于基因表达的光遗传学致动器。需要复杂的生物医学技术,包括外源基因工程、转染和材料递送。在这里,我们提出了一个全光学的方法来调节靶细胞中的基因表达。内源性或外源性基因可以通过飞秒激光照射的短闪光驱动的激活T细胞的Ca2+敏感性转录因子核因子(NFAT)来激活。当应用于间充质干细胞时,分化调节剂Osterix的表达可以通过该方法激活以潜在地诱导它们的分化。进一步开发了通过多次激光照射的激光诱导“Ca 2+梳”(LiCCo),以提高基因表达效率。因此,这种非侵入性的方法提供了一个令人鼓舞的进展,基因表达调控,具有广阔的潜力,应用于细胞生物学和干细胞科学。
Controllable gene expression is always a challenge and of great significance to biomedical research and clinical applications. Recently, various approaches based on extra-engineered light-sensitive proteins have been developed to provide optogenetic actuators for gene expression. Complicated biomedical techniques including exogenous genes engineering, transfection and material delivery are needed. Here we present an all-optical method to regulate gene expression in targeted cells. Intrinsic or exogenous genes can be activated by a Ca2+-sensitive transcription factor nuclear factor of activated T cells (NFAT) driven by a short flash of femtosecond-laser irradiation. When applied to mesenchymal stem cells, expression of a differentiation regulator Osterix can be activated by this method to potentially induce differentiation of them. A laser-induced “Ca2+-comb” (LiCCo) by multi-time laser exposure is further developed to enhance gene expression efficiency. This noninvasive method hence provides an encouraging advance of gene expression regulation, with promising potential of applying in cell biology and stem-cell science.
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