Genetically encoded assembly recorder temporally resolves cellular history
TL;DR
GEMINI is a genetically encoded protein assembly that records cellular history with hour-level accuracy, enabling retrospective imaging of dynamic processes like NFκB signaling and neuronal activity in tissues.
Key Takeaways
- •GEMINI uses a designed protein assembly to record cellular events as fluorescent patterns, similar to tree rings, for retrospective analysis.
- •It achieves hour-level chronological accuracy and can resolve fast dynamics down to 15 minutes, such as NFκB-mediated transcriptional changes.
- •The platform works in live cells and intact tissues, including mouse brains, with minimal impact on neuronal function, revealing spatial heterogeneity in signaling.
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Abstract
Cells constantly change their molecular state in response to internal and external cues1. Mapping cellular activity in tissues with spatiotemporal precision is essential for understanding organ physiology, pathology, and regenerative processes. Current cell-sensing modalities primarily rely on either endpoint analysis that takes static snapshots, or real-time sensing that monitors a small subset of cells3,4. Here, we introduce Granularly Expanding Memory for Intracellular Narrative Integration (GEMINI), an in cellulo recording platform that leverages a computationally designed protein assembly as an intracellular memory device to record the history of individual cells. GEMINI grows predictably within live cells, capturing cellular events as tree-ring-like fluorescent patterns for imaging-based retrospective readout. Absolute chronological information of activity histories is attainable with hour-level accuracy. GEMINI effectively maps differential NFκB-mediated transcriptional changes, resolving fast dynamics of 15 minutes and providing quantifiable signal amplitudes. In a xenograft model, GEMINI records inflammation-induced signaling dynamics across tissue, revealing spatial heterogeneity linked to vascular density. When expressed in the mouse brain, GEMINI minimally impacts neuronal functions and can resolve both transcriptional changes and activity patterns of neurons. Together, GEMINI provides a robust and generalizable means for spatiotemporal mapping of cell dynamics underlying physiological and pathological processes in both culture and intact tissues.
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Author information
Zhe Li
Present address: Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, China
These authors contributed equally: Yuqing Yan, Jiaxi Lu, Zhe Li
Authors and Affiliations
Department of Materials Science and Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA
Yuqing Yan, Jiaxi Lu, Zuohan Zhao, Yimei Wang, Hongru Yang, Aileen Qi, Yongzhi Sun & Dingchang Lin
Institute for NanoBiotechnology, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA
Yuqing Yan, Jiaxi Lu, Zuohan Zhao, Yimei Wang, Hongru Yang, Yongzhi Sun & Dingchang Lin
Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore, MD, USA
Yuqing Yan, Dwight E. Bergles & Dingchang Lin
Institute for Protein Design, University of Washington, Seattle, WA, USA
Zhe Li, Shunzhi Wang & David Baker
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
Timothy F. Shay & Yaping Lei
Solomon H. Snyder Department of Neuroscience, School of Medicine, Johns Hopkins University, Baltimore, MD, USA
Wei Chen, Patrick Parker & Dwight E. Bergles
Center for Cell Dynamics, School of Medicine, Johns Hopkins University, Baltimore, MD, USA
Dingchang Lin
- Yuqing Yan
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- Jiaxi Lu
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- Zhe Li
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- Zuohan Zhao
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- Timothy F. Shay
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- Shunzhi Wang
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- Yaping Lei
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- Yimei Wang
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- Wei Chen
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- Patrick Parker
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- Hongru Yang
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- Aileen Qi
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- Yongzhi Sun
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