Single-cell FM streaming using genetically encoded protein oscillators

Abstract

Wireless devices use frequency modulation (FM) to reliably transmit information. Here, we establish a biochemical analogue of this paradigm using genetically encoded protein oscillators (GEOs) as carrier signals for real-time streaming of single-cell data. The GEO platform leverages evolutionarily diverse MinDE-family ATPase and Activator modules to generate fast synthetic protein oscillations in cells, where the waveform is controlled by both circuit biochemistry and intrinsic cellular physiology. This allows for diverse data encoding strategies, including noise-resistant FM reporters that broadcast proteasomal degradation or transcriptional dynamics; and autoencoder circuits that directly couple shifts in cell physiology to GEO waveform. Deploying GEOs in human embryonic stem cells allowed us to track single-cell developmental states in living populations during differentiation, revealing distinct patterns of spatiotemporal heterogeneity along endoderm, mesoderm, and ectoderm trajectories. The GEO platform establishes a dynamically controllable biochemical carrier signal, unlocking new high-fidelity FM data-encoding paradigms for continuous single-cell analysis.