The gut microbiota instructs the hepatic endothelial cell transcriptome.

Hepatology Microbiome Transcriptomics

Journal

iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038

Informations de publication

Date de publication:
22 Oct 2021
Historique:
received: 14 01 2021
revised: 15 07 2021
accepted: 06 09 2021
entrez: 8 10 2021
pubmed: 9 10 2021
medline: 9 10 2021
Statut: epublish

Résumé

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.

Identifiants

pubmed: 34622147
doi: 10.1016/j.isci.2021.103092
pii: S2589-0042(21)01060-9
pmc: PMC8479694
doi:

Types de publication

Journal Article

Langues

eng

Pagination

103092

Informations de copyright

© 2021 The Author(s).

Déclaration de conflit d'intérêts

The authors declare no competing interests.

Références

J Immunol. 2014 Aug 15;193(4):1942-53
pubmed: 25000979
Blood. 2005 Apr 15;105(8):3178-84
pubmed: 15626732
Nature. 2017 May 18;545(7654):305-310
pubmed: 28489816
Science. 2003 Mar 28;299(5615):2074-6
pubmed: 12663928
Genome Biol. 2014;15(12):550
pubmed: 25516281
Nutrients. 2021 Jun 08;13(6):
pubmed: 34201382
Pathology. 2012 Apr;44(3):181-6
pubmed: 22406487
J Am Heart Assoc. 2016 Aug 30;5(9):
pubmed: 27577581
PLoS One. 2011;6(7):e21800
pubmed: 21789182
Cell Transplant. 2013;22(10):1801-11
pubmed: 23044355
J Cell Biochem. 2004 Aug 15;92(6):1075-85
pubmed: 15258893
Sci Transl Med. 2014 May 21;6(237):237ra66
pubmed: 24848256
Nat Rev Immunol. 2009 May;9(5):364-75
pubmed: 19390567
J Biol Chem. 2001 Apr 6;276(14):10627-33
pubmed: 11134047
Microb Cell. 2020 Jan 02;7(1):28-31
pubmed: 31921931
Nat Rev Gastroenterol Hepatol. 2018 Sep;15(9):555-567
pubmed: 29844586
Hepatology. 2009 Sep;50(3):909-19
pubmed: 19610048
Hepatology. 2009 Mar;49(3):998-1011
pubmed: 19085956
Genome Biol. 2015 Mar 28;16:62
pubmed: 25887251
Nat Med. 2010 Aug;16(8):887-96
pubmed: 20676107
Cell Mol Immunol. 2016 May;13(3):347-53
pubmed: 27041636
Cell. 2020 May 28;181(5):1080-1096.e19
pubmed: 32380006
Nat Commun. 2020 May 18;11(1):2471
pubmed: 32424203
Nat Rev Gastroenterol Hepatol. 2018 Jul;15(7):397-411
pubmed: 29748586
Bioinformatics. 1998;14(8):656-64
pubmed: 9789091
Aliment Pharmacol Ther. 2019 Oct;50(8):930-939
pubmed: 31342533
Science. 2005 Mar 25;307(5717):1955-9
pubmed: 15790854
mBio. 2019 Jan 29;10(1):
pubmed: 30696735
Nature. 2012 Mar 11;483(7391):627-31
pubmed: 22407318
Mol Metab. 2016 Oct 13;5(12):1162-1174
pubmed: 27900259
Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15451-5
pubmed: 12432102
Nat Med. 2016 Oct 06;22(10):1079-1089
pubmed: 27711063
Am J Physiol. 1961 Dec;201:1027-9
pubmed: 14008363
Mol Cell. 2020 May 21;78(4):584-596
pubmed: 32234490
PLoS Biol. 2013 Jul;11(7):e1001610
pubmed: 23874157
mBio. 2019 Oct 22;10(5):
pubmed: 31641089
Hepatol Res. 2016 Jul;46(8):794-803
pubmed: 26510996
Hepatology. 2017 Apr;65(4):1181-1195
pubmed: 27981604
Cell Host Microbe. 2019 Apr 10;25(4):553-564.e7
pubmed: 30974084
Hepatology. 2009 Nov;50(5):1617-24
pubmed: 19725107
Nat Med. 2010 Feb;16(2):228-31
pubmed: 20081863
Mediators Inflamm. 2015;2015:831059
pubmed: 26604433
Blood. 2013 Sep 19;122(12):2030-8
pubmed: 23884859
Curr Treat Options Gastroenterol. 2020 Jun;18(2):270-280
pubmed: 33716495
Science. 2017 Aug 25;357(6353):
pubmed: 28775214
Blood. 2017 Jul 27;130(4):542-553
pubmed: 28572286
Sci Rep. 2017 Mar 13;7:44356
pubmed: 28287163
J Biol Chem. 2017 Nov 24;292(47):19198-19208
pubmed: 28924047
Front Immunol. 2019 Jun 20;10:1404
pubmed: 31316501
J Innate Immun. 2019;11(5):393-404
pubmed: 30566939
Arterioscler Thromb Vasc Biol. 2020 Sep;40(9):2279-2292
pubmed: 32611241
Lancet. 2002 May 4;359(9317):1612-5
pubmed: 12047987
Am J Pathol. 1993 Feb;142(2):481-8
pubmed: 8434643
Hepatology. 2021 Jan;73(1):126-143
pubmed: 32794259
Biochem J. 2000 May 15;348 Pt 1:71-6
pubmed: 10794715
Annu Rev Immunol. 2012;30:69-94
pubmed: 22149932
Pflugers Arch. 2014 Jan;466(1):77-89
pubmed: 24196564
Mol Metab. 2014 Jan 08;3(2):155-66
pubmed: 24634828
J Clin Microbiol. 2000 Apr;38(4):1672-5
pubmed: 10747167

Auteurs

Henning Formes (H)

Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, Johannes Gutenberg-University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.
Department of Chemistry, Biochemistry, Johannes Gutenberg-University Mainz, Hanns-Dieter-Hüsch-Weg 17, 55128 Mainz, Germany.

Joana P Bernardes (JP)

Institute of Clinical Molecular Biology, Christian-Albrechts-University and University Medical Center Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.

Amrit Mann (A)

Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, Johannes Gutenberg-University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.

Franziska Bayer (F)

Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, Johannes Gutenberg-University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.

Giulia Pontarollo (G)

Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, Johannes Gutenberg-University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.

Klytaimnistra Kiouptsi (K)

Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, Johannes Gutenberg-University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.

Katrin Schäfer (K)

Department of Cardiology, Cardiology I, University Medical Center Mainz, Johannes Gutenberg-University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.
German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany.

Sebastian Attig (S)

Research Center for Immunotherapy (FZI), University Medical Center, Johannes Gutenberg-University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.
TRON, Translational Oncology at the University Medical Center, Johannes Gutenberg-University Mainz gGmbH, Freiligrathstrasse 12, 55131 Mainz, Germany.

Teodora Nikolova (T)

Institute of Toxicology, University Medical Center Mainz, Johannes Gutenberg-University Mainz, 55131 Mainz, Germany.

Thomas G Hofmann (TG)

Institute of Toxicology, University Medical Center Mainz, Johannes Gutenberg-University Mainz, 55131 Mainz, Germany.

Jörn M Schattenberg (JM)

Metabolic Liver Research Program, Department of Internal Medicine I, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.

Hristo Todorov (H)

Institute of Human Genetics, University Medical Center, Johannes Gutenberg-University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.

Susanne Gerber (S)

Institute of Human Genetics, University Medical Center, Johannes Gutenberg-University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.

Philip Rosenstiel (P)

Institute of Clinical Molecular Biology, Christian-Albrechts-University and University Medical Center Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.

Tobias Bopp (T)

Research Center for Immunotherapy (FZI), University Medical Center, Johannes Gutenberg-University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.
Institute for Immunology, University Medical Center Mainz, Johannes Gutenberg-University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.

Felix Sommer (F)

Institute of Clinical Molecular Biology, Christian-Albrechts-University and University Medical Center Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.

Christoph Reinhardt (C)

Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, Johannes Gutenberg-University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.
German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany.

Classifications MeSH