iScience (Oct 2021)

The gut microbiota instructs the hepatic endothelial cell transcriptome

  • Henning Formes,
  • Joana P. Bernardes,
  • Amrit Mann,
  • Franziska Bayer,
  • Giulia Pontarollo,
  • Klytaimnistra Kiouptsi,
  • Katrin Schäfer,
  • Sebastian Attig,
  • Teodora Nikolova,
  • Thomas G. Hofmann,
  • Jörn M. Schattenberg,
  • Hristo Todorov,
  • Susanne Gerber,
  • Philip Rosenstiel,
  • Tobias Bopp,
  • Felix Sommer,
  • Christoph Reinhardt

Journal volume & issue
Vol. 24, no. 10
p. 103092

Abstract

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Summary: The gut microbiota affects remote organ functions but its impact on organotypic endothelial cell (EC) transcriptomes remains unexplored. The liver endothelium encounters microbiota-derived signals and metabolites via the portal circulation. To pinpoint how gut commensals affect the hepatic sinusoidal endothelium, a magnetic cell sorting protocol, combined with fluorescence-activated cell sorting, was used to isolate hepatic sinusoidal ECs from germ-free (GF) and conventionally raised (CONV-R) mice for transcriptome analysis by RNA sequencing. This resulted in a comprehensive map of microbiota-regulated hepatic EC-specific transcriptome profiles. Gene Ontology analysis revealed that several functional processes in the hepatic endothelium were affected. The absence of microbiota influenced the expression of genes involved in cholesterol flux and angiogenesis. Specifically, genes functioning in hepatic endothelial sphingosine metabolism and the sphingosine-1-phosphate pathway showed drastically increased expression in the GF state. Our analyses reveal a prominent role for the microbiota in shaping the transcriptional landscape of the hepatic endothelium.

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