@article {69847, title = {Fast, accurate, and versatile data analysis platform for the quantification of molecular spatiotemporal signals.}, journal = {Cell}, year = {2025}, month = {2025 Apr 04}, abstract = {

Optical recording of intricate molecular dynamics is becoming an indispensable technique for biological studies, accelerated by the development of new or improved biosensors and microscopy technology. This creates major computational challenges to extract and quantify biologically meaningful spatiotemporal patterns embedded within complex and rich data sources, many of which cannot be captured with existing methods. Here, we introduce activity quantification and analysis (AQuA2), a fast, accurate, and versatile data analysis platform built upon advanced machine-learning techniques. It decomposes complex live-imaging-based datasets into elementary signaling events, allowing accurate and unbiased quantification of molecular activities and identification of consensus functional units. We demonstrate applications across a wide range of biosensors, cell types, organs, animal models, microscopy techniques, and imaging approaches. As exemplar findings, we show how AQuA2 identified drug-dependent interactions between neurons and astroglia, as well as distinct sensorimotor signal propagation patterns in the mouse spinal cord.

Preprint:\ https://doi.org/10.1101/2024.05.02.592259

}, issn = {1097-4172}, doi = {10.1016/j.cell.2025.03.012}, url = {https://doi.org/10.1016/j.cell.2025.03.012}, author = {Mi, Xuelong and Chen, Alex Bo-Yuan and Duarte, Daniela and Carey, Erin and Taylor, Charlotte R and Braaker, Philipp N and Bright, Mark and Almeida, Rafael G and Lim, Jing-Xuan and Ruetten, Virginia M S and Wang, Yizhi and Wang, Mengfan and Zhang, Weizhan and Zheng, Wei and Reitman, Michael E and Huang, Yongkang and Wang, Xiaoyu and Li, Lei and Deng, Hanfei and Shi, Song-Hai and Poskanzer, Kira E and Lyons, David A and Nimmerjahn, Axel and Ahrens, Misha B and Yu, Guoqiang} } @article {70084, title = {Imaging cellular activity simultaneously across all organs of a vertebrate reveals body-wide circuits}, journal = {bioRxiv}, year = {2025}, month = {2025 August 22}, abstract = {

All cells in an animal collectively ensure, moment-to-moment, the survival of the whole organism in the face of environmental stressors1,2. 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, 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 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 activity3.Using this platform to screen the dynamics of all 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 Microscopy4 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.

}, doi = {10.1101/2025.08.20.670374}, url = {https://www.biorxiv.org/content/early/2025/08/22/2025.08.20.670374.1}, author = {Ruetten, Virginia M. S. and Zheng, Wei and Siwanowicz, Igor and Mensh, Brett D. and Eddison, Mark and Hu, Amy and Chi, Yunfeng and Lemire, Andrew L. and Guo, Caiying and Kadobianskyi, Mykola and Renz, Marc and Lelek-Greskovic, Sara and He, Yisheng and Close, Kari and Ihrke, Gudrun and Dev, Aparna and Petruncio, Alyson and Wan, Yinan and Engert, Florian and Fishman, Mark C. and Judkewitz, Benjamin and Rubinov, Mikail and Keller, Philipp J. and Satou, Chie and Yu, Guoqiang and Tillberg, Paul W. and Sahani, Maneesh and Ahrens, Misha B.} }