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dc.contributor.author
González-Loyola, Alejandra
dc.contributor.author
Bovay, Esther
dc.contributor.author
Kim, Jaeryung
dc.contributor.author
Wyss Lozano, Tania
dc.contributor.author
Sabine, Amélie
dc.contributor.author
Renevey, Francois
dc.contributor.author
Arroz-Madeira, Silvia
dc.contributor.author
Rapin, Alexis
dc.contributor.author
Wypych, Tomasz P.
dc.contributor.author
Rota, Giorgia
dc.contributor.author
Durot, Stephan
dc.contributor.author
Velin, Dominique
dc.contributor.author
Marsland, Benjamin
dc.contributor.author
Guarda, Greta
dc.contributor.author
Delorenzi, Mauro
dc.contributor.author
Zamboni, Nicola
dc.contributor.author
Luther, Sanjiv A.
dc.contributor.author
Petrova, Tatiana V.
dc.date.accessioned
2022-01-19T08:11:33Z
dc.date.available
2022-01-19T08:11:33Z
dc.date.issued
2021-07-14
dc.identifier.issn
2375-2548
dc.identifier.other
10.1126/sciadv.abf4335
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/526766
dc.identifier.doi
10.3929/ethz-b-000498274
dc.description.abstract
The mechanisms maintaining adult lymphatic vascular specialization throughout life and their role in coordinating inter-organ communication to sustain homeostasis remain elusive. We report that inactivation of the mechanosensitive transcription factor Foxc2 in adult lymphatic endothelium leads to a stepwise intestine-to-lung systemic failure. Foxc2 loss compromised the gut epithelial barrier, promoted dysbiosis and bacterial translocation to peripheral lymph nodes, and increased circulating levels of purine metabolites and angiopoietin-2. Commensal microbiota depletion dampened systemic pro-inflammatory cytokine levels, corrected intestinal lymphatic dysfunction, and improved survival. Foxc2 loss skewed the specialization of lymphatic endothelial subsets, leading to populations with mixed, pro-fibrotic identities and to emergence of lymph node–like endothelial cells. Our study uncovers a cross-talk between lymphatic vascular function and commensal microbiota, provides single-cell atlas of lymphatic endothelial subtypes, and reveals organ-specific and systemic effects of dysfunctional lymphatics. These effects potentially contribute to the pathogenesis of diseases, such as inflammatory bowel disease, cancer, or lymphedema.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
American Association for the Advancement of Science
en_US
dc.rights.uri
http://creativecommons.org/licenses/by-nc/4.0/
dc.title
FOXC2 controls adult lymphatic endothelial specialization, function, and gut lymphatic barrier preventing multiorgan failure
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution-NonCommercial 4.0 International
dc.date.published
2021-07-16
ethz.journal.title
Science Advances
ethz.journal.volume
7
en_US
ethz.journal.issue
29
en_US
ethz.journal.abbreviated
Sci Adv
ethz.pages.start
eabf4335
en_US
ethz.size
22 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.grant
Metabolic programs of lymphatic endothelial cells and their disturbance in lymphedema
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Washington, DC
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02538 - Institut für Molekulare Systembiologie / Institute for Molecular Systems Biology::08839 - Zamboni, Nicola (Tit.-Prof.)
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02538 - Institut für Molekulare Systembiologie / Institute for Molecular Systems Biology::08839 - Zamboni, Nicola (Tit.-Prof.)
ethz.grant.agreementno
177191
ethz.grant.fundername
SNF
ethz.grant.funderDoi
10.13039/501100001711
ethz.grant.program
Sinergia
ethz.date.deposited
2021-07-29T03:30:38Z
ethz.source
BATCH
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2022-01-19T08:11:43Z
ethz.rosetta.lastUpdated
2022-03-29T17:40:51Z
ethz.rosetta.versionExported
true
dc.identifier.olduri
http://hdl.handle.net/20.500.11850/525501
dc.identifier.olduri
http://hdl.handle.net/20.500.11850/498274
ethz.COinS
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