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照亮生命的萌芽:光遗传学在干细胞研究与治疗中的应用

Shining Light on the Sprout of Life: Optogenetics Applications in Stem Cell Research and Therapy.

作者信息

Mirzapour Delavar Hadi, Karamzadeh Arezou, Pahlavanneshan Saghar

机构信息

Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

J Membr Biol. 2016 Jun;249(3):215-20. doi: 10.1007/s00232-016-9883-4. Epub 2016 Feb 26.

DOI:10.1007/s00232-016-9883-4
PMID:26920546
Abstract

Optogenetics is the integration of genetics and optics to achieve gain or loss of function of well-defined events in specific cells of living tissue. As a versatile tool, upon light illumination, it allows fast control of precisely defined events in biological systems from single cell to different parts of whole tissue in freely moving animals. Taking advantage of this method, a multitude of studies have been published to understand brain functions and dysfunctions. Although from the beginning, it has been used to target neurons within the neural networks and to understand how specific neurons contribute to brain function, it gradually has been extended to other fields of biology such as stem cell research and therapy. With a combination of optogenetics and stem cells, new opportunities were opened up in stem cell biology and also its integration in new circuit as a cell-based treatment strategy for more common disorders like neurodegenerative and cardiovascular one. Recently, some studies showed that engineered stem cells expressing exogenous light-activated opsins can be used in stem cell biology including tracking the differentiation of stem cells, functional analysis of embryonic stem cell-derived graft, and testing the functional integration of induced pluripotent stem cell-derived neurons. With the advent of non-invasive approach, such as transcranial excitation or inhibition, optogenetics also holds promise for non-invasive control of engineered stem cell.

摘要

光遗传学是遗传学与光学的结合,用于在活组织的特定细胞中实现明确事件的功能获得或丧失。作为一种多功能工具,在光照下,它能够快速控制生物系统中从单细胞到自由活动动物整个组织不同部位的精确定义事件。利用这种方法,已经发表了大量研究来理解大脑功能和功能障碍。尽管从一开始,它就被用于针对神经网络中的神经元,以了解特定神经元如何对大脑功能做出贡献,但它逐渐扩展到了生物学的其他领域,如干细胞研究和治疗。光遗传学与干细胞相结合,为干细胞生物学带来了新机遇,也为其作为针对神经退行性和心血管等更常见疾病的基于细胞的治疗策略整合到新回路中创造了机会。最近,一些研究表明,表达外源光激活视蛋白的工程干细胞可用于干细胞生物学,包括追踪干细胞的分化、分析胚胎干细胞衍生移植物的功能以及测试诱导多能干细胞衍生神经元的功能整合。随着非侵入性方法(如经颅激发或抑制)的出现,光遗传学也有望对工程干细胞进行非侵入性控制。

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Shining Light on the Sprout of Life: Optogenetics Applications in Stem Cell Research and Therapy.照亮生命的萌芽:光遗传学在干细胞研究与治疗中的应用
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Application of Optogenetics for Muscle Cells and Stem Cells.光遗传学在肌肉细胞和干细胞中的应用。
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Genetically Encoded Photoactuators and Photosensors for Characterization and Manipulation of Pluripotent Stem Cells.基因编码的光致动器和光传感器用于多能干细胞的表征和操作。

本文引用的文献

1
Regulation of neural gene transcription by optogenetic inhibition of the RE1-silencing transcription factor.通过光遗传学抑制RE1沉默转录因子对神经基因转录的调控
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Rapid Conversion of Fibroblasts into Functional Forebrain GABAergic Interneurons by Direct Genetic Reprogramming.通过直接遗传重编程将成纤维细胞快速转化为功能性大脑 GABA 能中间神经元。
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Optogenetics for in vivo cardiac pacing and resynchronization therapies.光遗传学在体内心脏起搏和再同步治疗中的应用。
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Optogenetic control of insulin secretion by pancreatic β-cells in vitro and in vivo.体外和体内通过光遗传学控制胰岛β细胞胰岛素分泌。
Gene Ther. 2015 Jul;22(7):553-9. doi: 10.1038/gt.2015.23. Epub 2015 Mar 26.
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Induced pluripotent stem cells: applications in regenerative medicine, disease modeling, and drug discovery.诱导多能干细胞:在再生医学、疾病建模和药物发现中的应用。
Front Cell Dev Biol. 2015 Feb 2;3:2. doi: 10.3389/fcell.2015.00002. eCollection 2015.
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Optogenetics enables functional analysis of human embryonic stem cell-derived grafts in a Parkinson's disease model.光遗传学能够在帕金森病模型中对人胚胎干细胞衍生移植物进行功能分析。
Nat Biotechnol. 2015 Feb;33(2):204-9. doi: 10.1038/nbt.3124. Epub 2015 Jan 12.
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Activated astrocytes enhance the dopaminergic differentiation of stem cells and promote brain repair through bFGF.活化的星形胶质细胞通过碱性成纤维细胞生长因子增强干细胞的多巴胺能分化并促进脑修复。
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Human ESC-derived dopamine neurons show similar preclinical efficacy and potency to fetal neurons when grafted in a rat model of Parkinson's disease.当移植到帕金森病大鼠模型中时,人胚胎干细胞衍生的多巴胺神经元显示出与胎儿神经元相似的临床前疗效和效力。
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