Permeability-driven pressure and cell proliferation control lumen morphogenesis in pancreatic organoids

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Byung Ho Lee - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Kana Fuji - , The University of Tokyo (Author)
  • Heike Petzold - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Phil Seymour - , Novo Nordisk Foundation Center for Stem Cell Biology (Author)
  • Siham Yennek - , Novo Nordisk Foundation Center for Stem Cell Biology (Author)
  • Coline Schewin - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Allison Lewis - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Daniel Riveline - , University of Strasbourg (Author)
  • Tetsuya Hiraiwa - , The University of Tokyo, Academia Sinica - Institute of Physics, National University of Singapore (Author)
  • Masaki Sano - , The University of Tokyo, Shanghai Jiao Tong University (Author)
  • Anne Grapin-Botton - , Max Planck Institute of Molecular Cell Biology and Genetics, Paul Langerhans Institute Dresden (PLID) of the Helmholtz Center Munich, Clusters of Excellence PoL: Physics of Life (Author)

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.

Details

Original languageEnglish
Pages (from-to)113–124
Number of pages12
JournalNature cell biology
Volume28
Issue number1
Publication statusPublished - 19 Dec 2025
Peer-reviewedYes

External IDs

PubMed 41419573

Keywords

ASJC Scopus subject areas