Optogenetic Control of the BMP Signaling Pathway,ACS Synthetic Biology

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Optogenetic Control of the BMP Signaling Pathway
ACS Synthetic Biology ( IF 3.7 ) Pub Date : 2020-10-21 , DOI: 10.1021/acssynbio.0c00315
Paul A Humphreys _{1,

2} , Steven Woods ₁ , Christopher A Smith ₁ , Nicola Bates ₁ , Stuart A Cain ₁ , Robert Lucas ₂ , Susan J Kimber ₁

Affiliation

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor β (TGFβ) superfamily and have crucial roles during development; including mesodermal patterning and specification of renal, hepatic, and skeletal tissues. In vitro developmental models currently rely upon costly and unreliable recombinant BMP proteins that do not enable dynamic or precise activation of the BMP signaling pathway. Here, we report the development of an optogenetic BMP signaling system (optoBMP) that enables rapid induction of the canonical BMP signaling pathway driven by illumination with blue light. We demonstrate the utility of the optoBMP system in multiple human cell lines to initiate signal transduction through phosphorylation and nuclear translocation of SMAD1/5, leading to upregulation of BMP target genes including Inhibitors of DNA binding ID2 and ID4. Furthermore, we demonstrate how the optoBMP system can be used to fine-tune activation of the BMP signaling pathway through variable light stimulation. Optogenetic control of BMP signaling will enable dynamic and high-throughput intervention across a variety of applications in cellular and developmental systems.

中文翻译：

BMP 信号通路的光遗传学控制

骨形态发生蛋白 (BMP) 是转化生长因子 β (TGFβ) 超家族的成员，在发育过程中发挥着至关重要的作用；包括肾、肝和骨骼组织的中胚层模式和规格。目前，体外发育模型依赖于昂贵且不可靠的重组 BMP 蛋白，这些蛋白无法动态或精确地激活 BMP 信号通路。在这里，我们报告了光遗传学 BMP 信号系统 (optoBMP) 的开发，该系统能够快速诱导由蓝光照射驱动的经典 BMP 信号通路。我们证明了 optoBMP 系统在多种人类细胞系中的实用性，可通过 SMAD1/5 的磷酸化和核转位启动信号转导，从而导致 BMP 靶基因（包括DNA 结合 ID2和ID4的抑制剂）的上调。此外，我们还演示了如何使用 optoBMP 系统通过可变光刺激来微调 BMP 信号通路的激活。 BMP 信号传导的光遗传学控制将能够在细胞和发育系统的各种应用中进行动态和高通量干预。

更新日期：2020-11-21

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