Screening-Based Chemical Approaches to Unravel Stem Cell Biology

Cell-permeable compounds provide a convenient and efficient approach to manipulate biological processes. A number of compounds controlling stem cell self-renewal, survival, differentiation, and reprogramming have been identified through high-throughput/content screens. Using these powerful chemical tools, strategies have been developed to direct human pluripotent stem cell (hPSC) differentiation to functional cells. Recently, hPSC-derived cells and organoids are used to model human diseases, which can be adapted to a high-throughput/content platform for chemical screens. The identified compounds provide novel tools for decoding the signaling pathways regulating disease progression and candidates for facilitating future drug discovery. Moreover, humanized mouse models carrying hPSC-derived cells enable an innovative system to evaluate the long-term in vivo efficacy of drug candidates on human cells. In summary, screening-based chemical approaches not only expedite strategy development of controlling stem cell fates, but also provide powerful tools for dissecting the molecular mechanisms regulating disease progression. : In this article, Chen et al. summarized the recent efforts to apply screen approach to identify small molecules controlling stem cell fates, and to establish hPSC-derived cells and organoids-based platforms for disease modeling and drug screening. Keywords: high-throughput screen, high-content screen, human pluripotent stem cells, directed differentiation, self-renewal, survival, reprogramming, organoids, disease modeling, drug discover