In this study, researchers utilized high-content, image-based screening to investigate the development and morphogenesis of human pancreatic organoids. By testing a library of small molecules, they identified 54 compounds that significantly alter cellular identity and physical structure, specifically focusing on the role of GSK3 inhibitors. The scientists discovered that activating WNT signaling while simultaneously suppressing FGF signaling drives pancreatic progenitors to differentiate into functional acinar cells. These findings are critical for understanding human organogenesis because acinar cells are the suspected site of origin for pancreatic cancer. The research ultimately provides a robust methodological framework for using automated imaging and multivariate analysis to study complex, heterogeneous organoid models.

References:

• Keshara R, Kuodyte K, Janosch A, et al. High-content screening of organoids reveals the mechanisms of human pancreas acinar specification[J]. Cell Stem Cell, 2026.