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

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Byung Ho Lee - , Max-Planck-Institut für molekulare Zellbiologie und Genetik (Autor:in)
  • Kana Fuji - , The University of Tokyo (Autor:in)
  • Heike Petzold - , Max-Planck-Institut für molekulare Zellbiologie und Genetik (Autor:in)
  • Phil Seymour - , Novo Nordisk Foundation Center for Stem Cell Biology (Autor:in)
  • Siham Yennek - , Novo Nordisk Foundation Center for Stem Cell Biology (Autor:in)
  • Coline Schewin - , Max-Planck-Institut für molekulare Zellbiologie und Genetik (Autor:in)
  • Allison Lewis - , Max-Planck-Institut für molekulare Zellbiologie und Genetik (Autor:in)
  • Daniel Riveline - , Université de Strasbourg (Autor:in)
  • Tetsuya Hiraiwa - , The University of Tokyo, Academia Sinica - Institute of Physics, National University of Singapore (Autor:in)
  • Masaki Sano - , The University of Tokyo, Shanghai Jiao Tong University (Autor:in)
  • Anne Grapin-Botton - , Max-Planck-Institut für molekulare Zellbiologie und Genetik, Paul Langerhans Institut Dresden (PLID) des Helmholtz Zentrum München, Exzellenzcluster PoL: Physik des Lebens (Autor:in)

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

OriginalspracheEnglisch
Seiten (von - bis)113–124
Seitenumfang12
FachzeitschriftNature cell biology
Jahrgang28
Ausgabenummer1
PublikationsstatusVeröffentlicht - 19 Dez. 2025
Peer-Review-StatusJa

Externe IDs

PubMed 41419573

Schlagworte

ASJC Scopus Sachgebiete