Generative AI for Cell Type-Specific Fluorescence Image Generation of hPSC-derived Cardiac Organoid.

Human pluripotent stem cell (hPSC)-derived cardiac organoid is the most recent three-dimensional tissue structure that mimics the structure and functionality of the human heart and plays a pivotal role in modeling heart development and disease. The hPSC-derived cardiac organoids are commonly characterized by bright-field microscopic imaging for tracking daily organoid differentiation and morphology formation. Although the brightfield microscope provides essential information about hPSC-derived cardiac organoids, such as morphology, size, and general structure, it does not extend our understanding of cardiac organoids on cell type-specific distribution and structure. Then, fluorescence microscopic imaging is required to identify the specific cardiovascular cell types in the hPSC-derived cardiac organoids by fluorescence immunostaining fixed organoid samples or fluorescence reporter imaging of live organoids. Both approaches require extra steps of experiments and techniques and do not provide general information on hPSC-derived cardiac organoids from different batches of differentiation and characterization, which limits the biomedical applications of hPSC-derived cardiac organoids. This research addresses this limitation by proposing a comprehensive workflow for colorizing phase contrast images of cardiac organoids from brightfield microscopic imaging using conditional Generative Adversarial Networks (GANs) to provide cardiovascular cell type-specific information in hPSC-derived cardiac organoids. By infusing these phase contrast images with accurate fluorescence colorization, our approach aims to unlock the hidden wealth of cell type, structure, and further quantifications of fluorescence intensity and area, for better characterizing hPSC-derived cardiac organoids.