Imaging cellular activity across all organs reveals body-wide circuits
8 affiliations
- 1Janelia Research Campus, HHMI, Ashburn, VA USA
- 2Gatsby Computational Neuroscience Unit, UCL, London, UK
- 3Virginia Tech, Blacksburg, VA USA
- 4Tsinghua University, Beijing, China
- 5Charité Universitätsmedizin Berlin, Berlin, Germany
- 6Harvard University, Cambridge, MA USA
- 7Biozentrum, University of Basel, Basel, Switzerland
- 8Vanderbilt University, Nashville, TN USA
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.
Related
- Label-free multimodal nonlinear optical imaging reveals key biomarkers of cellular radiation response
- A Single-Cell Atlas of PVOD Across the Lifespan Reveals Cellular and Molecular Therapeutic Targets
- FISIA, an information-based imaging tool, uncovers new spatial distributional patterns in neural circuits beyond fluorescence intensity
- The NuRD complex shapes RNA polymerase III activity at highly expressed tRNA gene clusters, tuning the dynamic range of cellular tRNA pools
- Translocation-induced enhancer rewiring reveals cryptic oncogenic circuits in multiple myeloma
BibTeX
@article{ruetten2026imaging,
title = {{Imaging cellular activity across all organs reveals body-wide circuits}},
author = {Virginie M. S. Ruetten and Wei Zheng and Igor Siwanowicz and Brett D. Mensh and Mark Eddison and Amy Hu and Yunfeng Chi and Andrew L. Lemire and Caiying Guo and Mykola Kadobianskyi and Marc Renz and Sara Lelek-Greskovic and Yisheng He and Kari Close and Gudrun Ihrke and Aparna Dev and Alyson Petruncio and Yinan Wan and Rongwei Zhang and Mark C. Fishman and Florian Engert and Benjamin Judkewitz and Mikail Rubinov and Philipp J. Keller and Chie Satou and Guoqiang Yu and Paul W. Tillberg and Maneesh Sahani and Misha B. Ahrens},
journal = {Nature},
year = {2026},
month = sep,
doi = {10.1038/s41586-026-10979-6},
url = {https://doi.org/10.1038/s41586-026-10979-6},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Imaging cellular activity across all organs reveals body-wide circuits
AU - Virginie M. S. Ruetten
AU - Wei Zheng
AU - Igor Siwanowicz
AU - Brett D. Mensh
AU - Mark Eddison
AU - Amy Hu
AU - Yunfeng Chi
AU - Andrew L. Lemire
AU - Caiying Guo
AU - Mykola Kadobianskyi
AU - Marc Renz
AU - Sara Lelek-Greskovic
AU - Yisheng He
AU - Kari Close
AU - Gudrun Ihrke
AU - Aparna Dev
AU - Alyson Petruncio
AU - Yinan Wan
AU - Rongwei Zhang
AU - Mark C. Fishman
AU - Florian Engert
AU - Benjamin Judkewitz
AU - Mikail Rubinov
AU - Philipp J. Keller
AU - Chie Satou
AU - Guoqiang Yu
AU - Paul W. Tillberg
AU - Maneesh Sahani
AU - Misha B. Ahrens
PY - 2026
DA - 2026/09/09
JO - Nature
DO - 10.1038/s41586-026-10979-6
UR - https://doi.org/10.1038/s41586-026-10979-6
AB - 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.
SN - 0028-0836
SN - 1476-4687
ER -