Game of zones: WNTer is coming

Datum

22.09.2026

Zeit

11:00 - 12:00

Sprecher

Jan Tchorz

Zugehörigkeit

Institute of Physiology, University of Tübingen, Germany

Sprache

en

Hauptthema

Biologie

Host

Meritxell Huch

Beschreibung

Complex organ function arises from spatially coordinated cell identities. Liver function depends on segregated metabolic programs along the porto-central axis. How this spatial logic and multicellular dynamics are disrupted in human chronic liver disease (CLD) remains unknown. By combining complex lineage tracing in mice and multimodal spatial transcriptomics in patients, we show that CLD across diverse etiologies is defined by a global collapse of metabolic zonation. Using spatial neighborhood analyses, we develop an entropy-based framework that quantitatively captures disruption of metabolic order and multicellular dynamics across three CLD etiologies. Mechanistically, impaired zonated WNT/β-catenin signaling drives loss of pericentral metabolism, whereas ectopic enrichment of WNT/RSPO ligands within injury niches induces transient metabolic reprogramming and hepatocyte plasticity during regeneration. YAP signaling promotes hepatocyte proliferation and induces biliary metaplasia in periportal hepatocytes, but therapeutic targeting of the pathway fails to restore liver regeneration following extended hepatectomy. Together, these findings demonstrate that hepatocyte identity and zonation are fundamentally fluid. Restoring functional tissue in chronic liver failure requires looking beyond static cell populations to target the underlying spatial signaling architectures that constrain aberrant plasticity and license productive organ regeneration.

Letztmalig verändert: 25.08.2026, 07:37:48