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Single cell-resolved study of advanced murine MASH reveals a homeostatic pericyte signaling module by Sofie M. Bendixen; Peter R. Jakobsgaard; Daniel Hansen; Kamilla H. Hejn; Mike K. Terkelsen; Frederik A. Bjerre; Annemette P. Thulesen; Niels G. Eriksen; Philip Hallenborg; Yana Geng; Trine V. Dam; Frederik T. Larsen; Charlotte W. Wernberg; Janusa Vijayathurai; Emma A.H. Scott; Ann-Britt Marcher; Sönke Detlefsen; Lars Grøntved; Henrik Dimke; Rebecca Berdeaux; Thomas Q. de Aguiar Vallim; Peter Olinga; Mette M. Lauridsen; Aleksander Krag; Blagoy Blagoev; Kim Ravnskjaer is a Medicine article available to read on EtoBox.

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## Highlights NR1H4/FXR is highly expressed in stellate cells of human and murine livers. NR1H4 binding motifs are highly enriched in stellate cell accessible chromatin. The NR1H4 agonist obeticholic acid upholds expression of stellate cell identity genes. Stellate cell-confined expression of G S PCR VIPR1 is attenuated in MASH livers. cAMP induces stellate cell expression of homeostatic factor GDF2 in vitro and in vivo. ## Impact and implications Homeostatic interactions between hepatic cell types and their deterioration in metabolic dysfunction-associated steatohepatitis are poorly characterized. In our current single cell-resolved study of advanced murine metabolic dysfunction-associated steatohepatitis, we identified a quiescence-associated hepatic stellate cell-signaling module with potential to preserve normal sinusoid function. As expression levels of its constituents are conserved in the human liver, stimulation of the identified signaling module is a promising therapeutic strategy to restore sinusoid function in chronic liver disease.

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Author

Sofie M. Bendixen; Peter R. Jakobsgaard; Daniel Hansen; Kamilla H. Hejn; Mike K. Terkelsen; Frederik A. Bjerre; Annemette P. Thulesen; Niels G. Eriksen; Philip Hallenborg; Yana Geng; Trine V. Dam; Frederik T. Larsen; Charlotte W. Wernberg; Janusa Vijayathurai; Emma A.H. Scott; Ann-Britt Marcher; Sönke Detlefsen; Lars Grøntved; Henrik Dimke; Rebecca Berdeaux; Thomas Q. de Aguiar Vallim; Peter Olinga; Mette M. Lauridsen; Aleksander Krag; Blagoy Blagoev; Kim Ravnskjaer

Publisher

Elsevier BV

Published

2024

Language

EN

Field

Medicine (Health Sciences)