Development of quantitative direct prediction algorithm for the human target organ similarity of human pluripotent stem cell-derived organoids and cells

Human pluripotent stem cell (hPSC)-derived organoids and differentiated cells have similar characteristics, such as cell types, structure, and functions, to human organs and tissues. Thus, in vitro human organoids and tissue-specific cells serve as a superior alternative to conventional cell lines and animal models in drug development and regenerative medicine. However, since hPSC-derived organoids and differentiated cells show fetal-like features, further differentiation and maturation methods have been developed for the generation of high-quality in vitro models of the corresponding human organs and tissues. Therefore, for a simple and reproducible analysis of the quality of organoids and cells to compensate for the shortcomings of existing experimental validation studies, a quantitative evaluation method should be developed. In this study, using the GTEx database (a total of 8,555 samples in 53 tissues), we constructed a quantitative calculation system (organ-specific panels and calculation algorithm) to assess the similarity to the human lung, stomach, and heart and confirmed the algorithm using in-house RNA-seq data (total RNA from 20 tissues). To evaluate our system, we generated hPSC-derived lung organoids, gastric organoids, and cardiomyocytes and detected 33.4%, 51.7%, and 83.4% similarity, respectively, to the corresponding human target organs. To facilitate access and use of our system for researchers, we developed the web-based user interface (Web-based Similarity Analysis System, W-SAS; for liver, lung, stomach, and heart) presenting similarity to the appropriate organs as percentages and specific gene expression patterns. Thus, the W-SAS system could provide valuable information for the generation of high-quality and readily available organoids/cells differentiated from hPSCs and a strategy to guide proper lineage-oriented differentiation.