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# Imaging cellular activity across all organs reveals body-wide circuits

## Details

**Authors** Virginie M. S. Ruetten et al.

**Year** 2026

**Publisher** Nature

**Kind of work** article

**Discipline** Physiology

**Secondary disciplines** Neuroscience

[Read it at the publisher](https://doi.org/10.1038/s41586-026-10979-6) 
10.1038/s41586-026-10979-6

## In authors' words

### 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 sensors, 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 microscopy. 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.

### What they set out to do (purpose)

Develop a whole-vertebrate-body live-imaging method to capture cellular activity simultaneously across all organs.

### Who or what was studied (sample)

Larval zebrafish (primary model) and adult Danionella cerebrum (proof of concept).

### How they did it (methods)

New microscopy and machine-learning method (WHOLISTIC) combining volumetric fluorescence imaging, pancellular calcium-sensor expression, whole-body expansion microscopy, and optogenetics.

### What they found (results)

Simultaneous whole-body imaging revealed previously unknown physiological couplings, including brainstem-controlled body-wide blood-flow redistribution and cross-organ muscle synergies, that are invisible to single-organ imaging, and optogenetic manipulation confirmed a causal brain-to-body driving effect.

## Commentary

### In short

The finding shows that only by observing an organism as a whole system across cellular, organ, and multi-organ scales, rather than any single organ or cell type in isolation, do certain causal cross-organ relationships become visible, illustrating how the observational vantage point determines what structure can be seen.

**Patterns it shows** S, R, P

**Added** 2026-09-16

**How to cite this** Virginie M. S. Ruetten et al. (2026). Imaging cellular activity across all organs reveals body-wide circuits. Nature.