Inducible tricolor reporter mouse for parallel imaging of lysosomes, mitochondria, and microtubules

Cell type-specific use of the same DNA blueprint generates diverse cell types. Such diversity must also be executed via differential deployment of the same subcellular machinery. However, our understanding of the size, distribution, and dynamics of subcellular machinery in native tissues and their connection to cellular diversity remains limited. We generate and characterize an inducible tricolor reporter mouse, dubbed "Kaleidoscope," for simultaneous imaging of lysosomes, mitochondria, and microtubules in any cell type and at a single-cell resolution. The expected subcellular compartments are labeled in culture and in tissues with no impact on cellular and organismal viability. Quantitative and live imaging of the tricolor reporter captures cell type-specific organelle features and kinetics in the lung, as well as their changes after Sendai virus infection. Yap/Taz mutant lung epithelial cells undergo accelerated lamellar body maturation, a subcellular manifestation of their molecular defects. A comprehensive toolbox of reporters for all subcellular structures is expected to transform our understanding of cell biology in tissues.