6533b7d4fe1ef96bd12634ce
RESEARCH PRODUCT
The gut microbiota instructs the hepatic endothelial cell transcriptome
Giulia PontarolloChristoph ReinhardtSusanne GerberSebastian AttigFelix SommerFranziska BayerHristo TodorovJörn M. SchattenbergJoana P. BernardesTobias BoppTeodora NikolovaKlytaimnistra KiouptsiHenning FormesThomas G. HofmannAmrit MannKatrin SchäferPhilip Rosenstielsubject
MultidisciplinaryHepatologybiologyEndotheliumAngiogenesisScienceQGut floraCell sortingbiology.organism_classificationArticleCell biologyTranscriptomeEndothelial stem cellmedicine.anatomical_structuremedicineMicrobiomeMicrobiomeTranscriptomicsGenedescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2021-10-01 | iScience |