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dc.contributor.author
Tacconi, Carlotta
dc.contributor.author
He, Yuliang
dc.contributor.author
Ducoli, Luca
dc.contributor.author
Detmar, Michael
dc.date.accessioned
2021-03-05T09:45:06Z
dc.date.available
2020-09-24T06:09:00Z
dc.date.available
2020-09-24T07:46:21Z
dc.date.available
2021-03-05T09:45:06Z
dc.date.issued
2021-02
dc.identifier.other
10.1007/s10456-020-09743-9
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/442173
dc.identifier.doi
10.3929/ethz-b-000442173
dc.description.abstract
Lymphatic and blood vascular endothelial cells (ECs) share several molecular and developmental features. However, these two cell types possess distinct phenotypic signatures, reflecting their different biological functions. Despite significant advances in elucidating how the specification of lymphatic and blood vascular ECs is regulated at the transcriptional level during development, the key molecular mechanisms governing their lineage identity under physiological or pathological conditions remain poorly understood. To explore the epigenomic signatures in the maintenance of EC lineage specificity, we compared the transcriptomic landscapes, histone composition (H3K4me3 and H3K27me3) and DNA methylomes of cultured matched human primary dermal lymphatic and blood vascular ECs. Our findings reveal that blood vascular lineage genes manifest a more ‘repressed’ histone composition in lymphatic ECs, whereas DNA methylation at promoters is less linked to the differential transcriptomes of lymphatic versus blood vascular ECs. Meta-analyses identified two transcriptional regulators, BCL6 and MEF2C, which potentially govern endothelial lineage specificity. Notably, the blood vascular endothelial lineage markers CD34, ESAM and FLT1 and the lymphatic endothelial lineage markers PROX1, PDPN and FLT4 exhibited highly differential epigenetic profiles and responded in distinct manners to epigenetic drug treatments. The perturbation of histone and DNA methylation selectively promoted the expression of blood vascular endothelial markers in lymphatic endothelial cells, but not vice versa. Overall, our study reveals that the fine regulation of lymphatic and blood vascular endothelial transcriptomes is maintained via several epigenetic mechanisms, which are crucial to the maintenance of endothelial cell identity.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Springer
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Blood endothelial cells
en_US
dc.subject
Lymphatic endothelial cells
en_US
dc.subject
Cell identity
en_US
dc.subject
Epigenetics
en_US
dc.subject
DNA methylation
en_US
dc.subject
Histone modifcations
en_US
dc.title
Epigenetic regulation of the lineage specificity of primary human dermal lymphatic and blood vascular endothelial cells
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2020-09-12
ethz.journal.title
Angiogenesis
ethz.journal.volume
24
en_US
ethz.journal.issue
1
en_US
ethz.pages.start
67
en_US
ethz.pages.end
82
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.grant
The role of lymphatic vessels in cancer progression
en_US
ethz.grant
Role of lymphatic vessels in cancer progression
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Dordrecht
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02534 - Institut für Pharmazeutische Wiss. / Institute of Pharmaceutical Sciences::03683 - Detmar, Michael (emeritus) / Detmar, Michael (emeritus)
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02534 - Institut für Pharmazeutische Wiss. / Institute of Pharmaceutical Sciences::03683 - Detmar, Michael (emeritus) / Detmar, Michael (emeritus)
ethz.grant.agreementno
166490
ethz.grant.agreementno
185392
ethz.grant.fundername
SNF
ethz.grant.fundername
SNF
ethz.grant.funderDoi
10.13039/501100001711
ethz.grant.funderDoi
10.13039/501100001711
ethz.grant.program
Projekte Lebenswissenschaften
ethz.grant.program
Exzellenzbeitrag in Lebenswissenschaften
ethz.date.deposited
2020-09-24T06:09:11Z
ethz.source
WOS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2021-03-05T09:45:20Z
ethz.rosetta.lastUpdated
2022-03-29T05:38:14Z
ethz.rosetta.versionExported
true
ethz.COinS
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