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.

肠道微生物群影响远程器官功能，但其对器官型内皮细胞 (EC) 转录组的影响仍有待探索。肝脏内皮通过门脉循环遇到微生物群衍生的信号和代谢物。为了查明肠道共生体如何影响肝窦内皮，使用磁性细胞分选方案与荧光激活细胞分选相结合，从无菌 (GF) 和常规培养 (CONV-R) 小鼠中分离肝窦内皮用于转录组通过 RNA 测序进行分析。这导致了微生物群调节的肝脏 EC 特异性转录组谱的综合图谱。基因本体分析显示肝内皮中的几个功能过程受到影响。微生物群的缺失影响了参与胆固醇流动和血管生成的基因的表达。具体而言，在肝内皮鞘氨醇代谢和 1-磷酸鞘氨醇通路中起作用的基因在 GF 状态下表达急剧增加。我们的分析揭示了微生物群在塑造肝内皮转录景观方面的重要作用。