高解像度蛍光センサーで細胞内アデノシン動態を可視化(Researchers Develop High-resolution Fluorescent Sensor to Visualize Intracellular Adenosine Dynamics)

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2025-05-12 中国科学院(CAS)

高解像度蛍光センサーで細胞内アデノシン動態を可視化(Researchers Develop High-resolution Fluorescent Sensor to Visualize Intracellular Adenosine Dynamics)HypnoS: a Hypersensitive intracellular adenosine Sensor (Image by IGDB)

中国科学院と北京大学の研究チームは、細胞内アデノシン(iAdo)の動態をリアルタイムに可視化できる高感度蛍光センサー「HypnoS」を開発した。cpEGFPとアデノシンデアミナーゼを融合させたこのセンサーは、最大約900%の蛍光応答を持ち、てんかん発作や睡眠覚醒に関わるiAdoの変化を高精度で検出可能。マウスの脳での実験により、神経細胞とアストロサイトがiAdoを通じて睡眠調節に異なる役割を果たすことが示された。成果は『Nature Communications』誌に掲載。

<関連情報>

細胞内アデノシンの細胞種特異的制御を時空間的に明らかにする高性能蛍光センサー A high-performance fluorescent sensor spatiotemporally reveals cell-type specific regulation of intracellular adenosine in vivo

Qingpeng Wei,Zexiao Bai,Lei Wang,Jing Wang,Yipan Wang,Yufei Hu,Shiyi Ding,Zhixiong Ma,Chun Li,Yumo Li,Yizhou Zhuo,Wenzhe Li,Fei Deng,Bingjie Liu,Pengcheng Zhou,Yulong Li,Zhaofa Wu & Jing Wang
Nature Communications  Published:07 May 2025
DOI:https://doi.org/10.1038/s41467-025-59530-7

Abstract

Adenosine (Ado), a nucleoside bridging intracellular metabolism with intercellular communication, plays an essential role in regulating processes such as sleep and seizure. While the functions of extracellular Ado (“eAdo”) are well documented, our knowledge about the distribution and regulatory functions of intracellular Ado (“iAdo”) is limited by a lack of methods for detecting iAdo in vivo. Here, we develop HypnoS, a genetically encoded fluorescent sensor for iAdo characterized by its high sensitivity, specificity, spatiotemporal resolution, and rapid response (sub-seconds). HypnoS enables real-time visualization of iAdo dynamics in live cultures, acute brain slices, flies, and freely moving mice. Using HypnoS for dual-color mesoscopic imaging in mice, we show that seizure-induced iAdo waves propagated across the cortex, following calcium signals. Additionally, two-photon imaging reveals that iAdo decays more rapidly in astrocytes than in neurons during seizures. Moreover, by recording iAdo dynamics in the basal forebrain during the sleep-wake cycle, we observe that iAdo signals are present during wakefulness and rapid eye movement (REM) sleep, regulated by equilibrative nucleoside transporters (ENT1/2). Thus, HypnoS is a versatile and powerful tool for investigating the biological functions of iAdo across a range of physiological and pathological states.

細胞遺伝子工学
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