Scientists first observe whole-body cell communication via WHOLISTIC system
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Researchers published a study in Nature on September 9, 2026, introducing WHOLISTIC, a system that observes cell activity across the entire body with second-level resolution. The method uses genetically encoded calcium sensors and high-speed fluorescence microscopy in transparent zebrafish larvae and Danionella cerebrum. The system revealed previously unknown cellular responses, including cartilage reaction to cold and non-neuronal effects of ketamine.
Key Facts
- The study was published in Nature on September 9, 2026.
- WHOLISTIC uses genetically encoded calcium sensors to monitor cell activity across the whole body with second-level resolution.
- Experiments were conducted on transparent zebrafish larvae and adult Danionella cerebrum.
- The system revealed cartilage cells respond to cold and ketamine affects tissues beyond neurons.
- Researchers observed brainstem control of blood flow redistribution and rhythmic waves in kidney nephrons.
WHOLISTIC System
WHOLISTIC is a system designed to observe cellular activity across the entire organism with second-level resolution. The method relies on monitoring changes in intracellular calcium concentration, a key signaling molecule in processes from neuronal firing to muscle contraction. Through genetic engineering, researchers made nearly all cells in the organism produce fluorescent calcium sensors that light up when calcium levels change. High-speed fluorescence microscopy then captures these signals, allowing simultaneous observation of how different tissues and organs respond.
Overcoming Transparency Barriers
Previously, detailed observation of cellular activity was limited to individual tissues or organs, such as the brain. Most vertebrate tissues are opaque and scatter light, making it nearly impossible to image cells deep inside the body. To solve this, researchers used transparent vertebrates: zebrafish larvae and adult Danionella cerebrum. Their transparency allowed fluorescent signals to be recorded directly through the animal's body.
Unexpected Cellular Responses
The new technology revealed several previously unknown or poorly understood processes. Scientists discovered that cartilage cells respond to cold. Ketamine, an anesthetic, was found to affect not only neurons but also tissues at the boundary of the brain meninges. WHOLISTIC also identified previously unknown combinations of muscle group activity and connections between muscles and internal organs. Researchers observed the brainstem's role in redistributing blood flow throughout the body and rhythmic waves of activity in kidney nephrons.
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