2026年9月9日，美国霍华德?休斯医学研究所（HHMI）珍妮利亚研究园区Misha B. Ahrens等科学家在《自然》发表研究，开发了WHOLISTIC全身活体成像系统，对整个脊椎动物所有器官的细胞活动进行成像，揭示了全身回路。

动物的生存和繁荣能力——无论是逃离危险、进食还是对抗感染——都源于全身许多相互作用的细胞类型每时每刻的集体活动。生理学试图阐明这些跨越器官、细胞类型和时间尺度的细胞相互作用，但一直受限于无法同时记录整个身体中这种随时间变化的细胞活动。在此，研究人员开发了WHOLISTIC（记录组织和细胞内活动的全身活体成像系统），一种以细胞分辨率对整个脊椎动物身体中细胞秒级活动进行成像的方法。WHOLISTIC推进并整合了体积荧光显微镜、机器学习以及钙传感器的全细胞转基因表达，在斑马鱼幼鱼中进行了演示，并在成年Danionella cerebrum中进行了概念验证。为了获取与所测量动态相关的分子和超微结构基础信息，研究人员推进了全身扩张显微镜。在细胞尺度上，全身筛查揭示了意想不到的反应，包括软骨细胞对冷的反应和脑膜对氯胺酮的反应。在器官尺度上，WHOLISTIC识别出沿肾单位的有节律的行进波。在多器官尺度上，它揭示了未知的肌肉协同作用和肌肉-器官相互作用。在整个生物体尺度上，该方法捕获了脑干控制的全身血流重新分布。将光遗传学与WHOLISTIC相结合，实现了脑-身体相互作用的全光学因果解析。这些进展为系统生物学建立了一个范式，弥合了细胞生理学和机体生理学，使得能够跨尺度进行全面发现——从基本机制到治疗靶点。

附：英文原文

Title: Imaging cellular activity across all organs reveals body-wide circuits

Author: Ruetten, Virginie M. S., Zheng, Wei, Siwanowicz, Igor, Mensh, Brett D., Eddison, Mark, Hu, Amy, Chi, Yunfeng, Lemire, Andrew L., Guo, Caiying, Kadobianskyi, Mykola, Renz, Marc, Lelek-Greskovic, Sara, He, Yisheng, Close, Kari, Ihrke, Gudrun, Dev, Aparna, Petruncio, Alyson, Wan, Yinan, Zhang, Rongwei, Fishman, Mark C., Engert, Florian, Judkewitz, Benjamin, Rubinov, Mikail, Keller, Philipp J., Satou, Chie, Yu, Guoqiang, Tillberg, Paul W., Sahani, Maneesh, Ahrens, Misha B.

Issue&Volume: 2026-09-09

Abstract: An animal’s ability to survive and thrive—whether fleeing from danger, eating a meal, or fighting an infection—arises from the collective moment-to-moment activity of many interacting cell types throughout the body. Physiology seeks to elucidate these cellular interactions that span organs, cell types and timescales, but has been limited by the inability to record this time-varying cellular activity simultaneously throughout the entire body. Here we develop WHOLISTIC (WHole-Organism Live-Imaging System for recording Tissue and IntraCellular activity), a method to image second-timescale activity of cells across the entire vertebrate body at cellular resolution. WHOLISTIC advances and integrates volumetric fluorescence microscopy, machine learning, and pancellular transgenic expression of calcium sensors1, demonstrated in larval zebrafish, with proof of concept in adult Danionella cerebrum. To access information about the molecular and ultrastructural substrates for the measured dynamics, we advanced whole-body expansion microscopy2. At the cellular scale, body-wide screening revealed unexpected responses, including chondrocyte reactions to cold and meningeal responses to ketamine. At the organ scale, WHOLISTIC identified rhythmic travelling waves along the renal nephron. At the multi-organ scale, it revealed unknown muscle synergies and muscle–organ interactions. At the whole-organism scale, the method captured brainstem-controlled redistribution of body-wide blood flow. Combining optogenetics with WHOLISTIC enabled all-optical causal dissection of brain–body interactions. These advances establish a paradigm for systems biology that bridges cellular and organismal physiology, enabling comprehensive discovery across scales—from fundamental mechanisms to therapeutic targets.

DOI: 10.1038/s41586-026-10979-6

Source: https://www.nature.com/articles/s41586-026-10979-6