Haemodynamic control of zonated liver function via instructive vascular Wnt signalling.

Authors

Ki Hong Lee, Moritz Jakab, Alexey Uvarovskii, Dimitris Papageorgiou, Donato Inverso, Jingjing Shi, Maria Riedel, Stephanie Gehrs, Shubhada Kulkarni, Stefanie Bobe, Adnan Ali, Suchira Gallage, Sophia Siegmund, Johannes Gahn, Leon Blankenhorn, Michael Buettner, Gernot Poschet, Karsten Richter, Oksana Voloshanenko, Roxana Ola, Thomas Korff, Friedemann Kiefer, Mathias Heikenwalder, Michael Boutros, Christof Niehrs, Carolin Mogler, Jeroen Krijgsveld, Simon Anders, Hellmut G Augustin

Published in

Nature communications. Volume 17. Issue 1. Aug 22, 2026. Epub Aug 22, 2026.

Abstract

The vascular endothelium forms a systemically disseminated organ that translates micromilieu factors into instructive cues, designated as angiocrine signalling. While vascular control of organ function mechanisms have been discovered in essentially all major organs, the mechanisms of translating milieu factors into angiocrine signalling mechanisms remain largely elusive. Here, focussing on the well-established angiocrine Wnt signalling-regulated liver metabolic zonation paradigm, we identified blood flow-induced haemodynamic stress as a biophysical sensor that governs the angiocrine expression profile of liver sinusoidal endothelial cells (LSEC). Combining single-cell RNA sequencing with spatial proteomics, we generated a high-resolution crosstalk map of LSEC and hepatocytes from LSEC Wnt-deficient mutant mice and littermate controls. Intriguingly, vascular Wnt receptors, in parallel with angiocrine Wnt ligands, were specifically enriched in pericentral LSEC, enforcing the spatially coordinated vascular Wnt functions. Consequently, vascular Wnt further modulated angiocrine gene signatures, LSEC morphology, and the expression of gap junctional molecules in an autocrine manner. Taken together, the data define LSEC as a dynamic cellular decoder that translates biophysical forces into instructive angiocrine signals via activating promiscuous vascular Wnt factors.

PMID:
42632839
Bibliographic data and abstract were imported from PubMed on 23 Aug 2026.

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