Targeted and specific induction of cell death in an individual or groups of cells hold the potential for new insights into the response of tissues or organisms to different forms of death. Here, we report the development of optogenetically controlled cell death effectors (optoCDEs), a novel class of optogenetic tools that enables light-mediated induction of three types of programmed cell death (PCD)—apoptosis, pyroptosis, and necroptosis—using Arabidopsis thaliana photosensitive protein Cryptochrome-2. OptoCDEs enable a rapid and highly specific induction of PCD in human, mouse, and zebrafish cells and are suitable for a wide range of applications, such as sub-lethal cell death induction or precise elimination of single cells or cell populations in vitro and in vivo. As the proof-of-concept, we utilize optoCDEs to assess the differences in neighboring cell responses to apoptotic or necrotic PCD, revealing a new role for shingosine-1-phosphate signaling in regulating the efferocytosis of the apoptotic cell by epithelia.

中文翻译：

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细胞凋亡、坏死性凋亡和细胞焦亡的光遗传学激活剂


在个体或细胞群中定向和特异性诱导细胞死亡有可能为组织或生物体对不同形式死亡的反应提供新的见解。在这里，我们报告了光遗传学控制细胞死亡效应器（optoCDE）的开发，这是一类新型光遗传学工具，能够使用拟南芥光敏剂光介导诱导三种类型的程序性细胞死亡（PCD）——细胞凋亡、细胞焦亡和坏死性凋亡蛋白质隐花色素-2。 OptoCDE 能够在人类、小鼠和斑马鱼细胞中快速、高度特异性地诱导 PCD，适用于多种应用，例如亚致死细胞死亡诱导或体外和体内单细胞或细胞群的精确消除。作为概念验证，我们利用 optoCDE 评估邻近细胞对凋亡或坏死 PCD 反应的差异，揭示了 shingosine-1-磷酸信号在上皮细胞调节凋亡细胞胞吞作用中的新作用。