The gut microbiota instructs the hepatic endothelial cell transcriptome

被引：22

作者：

Formes, Henning ^{[1
,2
]}

Bernardes, Joana P. ^{[3
,4
]}

Mann, Amrit ^{[1
]}

Bayer, Franziska ^{[1
]}

Pontarollo, Giulia ^{[1
]}

Kiouptsi, Klytaimnistra ^{[1
]}

Schafer, Katrin ^{[5
,12
]}

Attig, Sebastian ^{[6
,7
]}

Nikolova, Teodora ^{[8
]}

Hofmann, Thomas G. ^{[8
]}

Schattenberg, Jorn M. ^{[9
]}

Todorov, Hristo ^{[10
]}

Gerber, Susanne ^{[10
]}

Rosenstiel, Philip ^{[3
,4
]}

Bopp, Tobias ^{[6
,11
]}

Sommer, Felix ^{[3
,4
]}

Reinhardt, Christoph ^{[1
,12
]}

机构：

[1] Johannes Gutenberg Univ Mainz, Univ Med Ctr Mainz, Ctr Thrombosis & Hemostasis CTH, Langenbeckstr 1, D-55131 Mainz, Germany

[2] Johannes Gutenberg Univ Mainz, Dept Chem, Biochem, Hanns Dieter Husch Weg 17, D-55128 Mainz, Germany

[3] Univ Kiel, Inst Clin Mol Biol, Campus Kiel, D-24105 Kiel, Germany

[4] Univ Med Ctr Schleswig Holstein, Campus Kiel, D-24105 Kiel, Germany

[5] Johannes Gutenberg Univ Mainz, Univ Med Ctr Mainz, Dept Cardiol, Cardiol 1, Langenbeckstr 1, D-55131 Mainz, Germany

[6] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Res Ctr Immunotherapy FZI, Langenbeckstr 1, D-55131 Mainz, Germany

[7] Johannes Gutenberg Univ Mainz gGmbH, Translat Oncol, TRON, Univ Med Ctr, Freiligrathstr 12, D-55131 Mainz, Germany

[8] Johannes Gutenberg Univ Mainz, Univ Med Ctr Mainz, Inst Toxicol, D-55131 Mainz, Germany

[9] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Internal Med 1, Metab Liver Res Program, Langenbeckstr 1, D-55131 Mainz, Germany

[10] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Human Genet, Langenbeckstr 1, D-55131 Mainz, Germany

[11] Johannes Gutenberg Univ Mainz, Univ Med Ctr Mainz, Inst Immunol, Langenbeckstr 1, D-55131 Mainz, Germany

[12] German Ctr Cardiovasc Res DZHK, Partner Site Rhine Main, Mainz, Germany

来源：

ISCIENCE | 2021年 / 24卷 / 10期

关键词：

MOUSE-LIVER; INFLAMMATION; CHOLESTEROL; IMMUNITY; SERUM; VIEW;

D O I：

10.1016/j.isci.2021.103092

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：18

共 58 条

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