Permeability-driven pressure and cell proliferation control lumen morphogenesis in pancreatic organoids
Year: 2025
Type: article
Abstract: Lumen formation in organ epithelia involves processes such as polarization, secretion, exocytosis and contractility, but what controls lumen shape remains unclear. Here we study how lumina develop spherical or complex structures using pancreatic organoids. Combining computational phase-field modelling and experiments, we found that lumen morphology depends on the balance between cell cycle duration and lumen pressure, low pressure and high proliferation produce complex shapes. Manipulating proliferation and lumen pressure can alter or reverse lumen development both in silico and in vitro. Increasing epithelial permeability reduces lumen pressure, converting from spherical to complex lumina. During pancreas development, the epithelium is initially permeable and becomes sealed, experimentally increasing permeability at late stages impairs ductal morphogenesis. Overall, our work underscores how proliferation, pressure and permeability orchestrate lumen shape, offering insights for tissue engineering and cystic disease treatment.
Source: Nature Cell Biology
Institutions: Max Planck Institute of Molecular Cell Biology and Genetics, The University of Tokyo, Novo Nordisk Foundation, Centre National de la Recherche Scientifique, Inserm, Institut de génétique et de biologie moléculaire et cellulaire, Université de Strasbourg, National University of Singapore, Institute of Physics, Academia Sinica, Mechanobiology Institute, Shanghai Jiao Tong University, Helmholtz Munich, Paul Langerhans Institute Dresden, Physics of Life, Technische Universität Dresden
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
OpenAlex ID: W4417492492