2026-01-21 マックス・プランク研究所
Pancreatic acinar organoid composed of polarized acinar cells displaying an enlarged Golgi complex (cyan) and expressing the digestive enzyme carboxypeptidase (magenta). The lumen enclosing fluid secreted by the cells is marked with phalloidin (yellow), cell nuclei are stained in blue.© Karolina Kuodyte/ Rashmiparvathi Keshara et al./ MPI-CBG
<関連情報>
- https://www.mpg.de/26028037/making-human-pancreatic-acinar-cells
- https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(25)00457-6
オルガノイドのハイコンテントスクリーニングによりヒト膵臓腺房の分化機構が明らかに High-content screening of organoids reveals the mechanisms of human pancreas acinar specification
Rashmiparvathi Keshara ∙ Karolina Kuodyte ∙ Antje Janosch ∙ … ∙ Rico Barsacchi ∙ Yung Hae Kim ∙ Anne Grapin-Botton
Cell Stem Cell Published:January 21, 2026
DOI:https://doi.org/10.1016/j.stem.2025.12.023
Highlights
- High-content screen reveals 54 compounds altering organoid shape or differentiation
- Analysis methods robust to organoid heterogeneity are established
- Screen-derived GSK3A/B inhibitors control pancreatic acinar cell differentiation
Summary
Organoids derived from pluripotent stem cells have emerged as powerful models to study human development. To investigate signaling pathways regulating human pancreas differentiation and morphogenesis, we developed a high-content, image-based screen and quantitative multivariate analysis pipelines robust to heterogeneity to extract single-cell and organoid features using pancreatic progenitor organoids. Here, we identified 54 compounds affecting cell identity and/or morphological landscape. Focusing on one family of compounds, we found that glycogen synthase kinase 3α/β (GSK3A/B) inhibition via wingless/int-1 (WNT) signaling has a reversible effect on cell identity, repressing pancreatic progenitor markers and inducing a poised state in progenitors transitioning to acinar cells. We show that additional fibroblast growth factor (FGF) repression enables further differentiation of acinar cells, recapitulating pancreatic acinar morphogenesis and function. The ability to produce acinar cells is valuable for future studies on pancreatic exocrine function and cancer initiation in humans, as acinar cells are thought to be an important cell of origin for pancreatic adenocarcinoma.
