Imaging cellular activity simultaneously across all organs of a vertebrate reveals body-wide circuits
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Le résumé fourni par la source
Abstract All cells in an animal collectively ensure, moment-to-moment, the survival of the whole organism in the face of environmental stressors 1,2 . Physiology seeks to elucidate the intricate network of interactions that sustain life, which often span multiple organs, cell types, and timescales, but a major challenge lies in the inability to simultaneously record time-varying cellular activity throughout the entire body. We developed WHOLISTIC (WHole Organism Live Imaging System for recording Tissue and IntraCellular activity), a method to image second-timescale, time-varying intracellular dynamics across cell-types of the vertebrate body. By advancing and integrating volumetric fluorescence microscopy, machine learning, and pancellular transgenic expression of calcium sensors in transparent young Danio rerio (zebrafish) and with proof of concept in adult Danionella , the method enables real-time recording of cellular dynamics across the organism. Calcium is a universal intracellular messenger, with a large array of cellular processes depending on changes in calcium concentration across varying time-scales, making it an ideal proxy of cellular activity 3 . Using this platform to screen the dynamics of most cells in the body, we discovered unexpected responses of specific cell types to stimuli, such as chondrocyte reactions to cold, meningeal responses to ketamine, and state-dependent activity, such as oscillatory ependymal-cell activity during periods of extended motor quiescence. At the organ scale, the method uncovered pulsating traveling waves along the kidney nephron. At the multi-organ scale, we uncovered muscle synergies and independencies, as well as muscle-organ interactions. Integration with optogenetics allowed us to all-optically determine the causal direction of brain-body interactions. At the whole-organism scale, the method captured the rapid brainstem-controlled redistribution of blood flow across the body. Finally, we advanced Whole-Body Expansion Microscopy 4 to provide ground-truth molecular and ultrastructural anatomical context, explaining the spatiotemporal structure of activity captured by WHOLISTIC. Together, these innovations establish a new paradigm for systems biology, bridging cellular and organismal physiology, with broad implications for both fundamental research and drug discovery.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Imaging cellular activity simultaneously across all organs of a vertebrate reveals body-wide circuits
- Date Crossref
- 21/08/2025
- Éditeur
- openRxiv
- Type
- posted-content
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
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Howard Hughes Medical Institute pays non établi dans la noticeStructure de recherche
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Janelia Research Campus pays non établi dans la noticeStructure de recherche
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Gatsby Computational Neuroscience Unit pays non établi dans la noticeStructure de recherche
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University College London pays non établi dans la noticeUniversité ou école supérieure
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Virginia Tech pays non établi dans la noticeUniversité ou école supérieure
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Charité - Universitätsmedizin Berlin pays non établi dans la noticeÉtablissement de santé
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Howard Hughes Medical Institute, Janelia Research Campus et Gatsby Computational Neuroscience Unit, avec 7 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.