V3Cell: A Vision-Guided Virtual 3D Cell Framework for Phenotypic Modeling and Perturbation Prediction

Predicting how organoids respond to chemical perturbations is central to disease modeling and drug discovery. Existing virtual cell models operate at the single-cell level, producing static endpoint predictions from destructive assays. This leaves a critical gap at the organoid scale, where biological identity is defined by tissue-level architecture and continuous developmental dynamics rather than single-cell features. Here we introduce V3Cell, a vision-guided framework that constructs in silico surrogates of organoids directly from non-invasive brightfield microscopy. A foreground-aware model constructs static virtual 3D cells across colon, stomach, and lung organoid lineages. These virtual 3D cells closely match real samples across distributional metrics, micro-texture, and lineage-specific morphometrics, with small effect sizes for most descriptors. A temporal module further predicts developmental fate from as few as six early-frame observations and models fate-conditioned spatiotemporal trajectories that closely recapitulate real perturbation responses. V3Cell requires no omics profiling or fluorescent labeling, establishing a non-invasive brightfield-based paradigm for organoid-scale perturbation prediction. Our code and data are publicly available at https://github.com/Laineyoulu/V3Cell.