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@ARTICLE{Schlereth:134840,
author = {K. Schlereth$^*$ and D. Weichenhan$^*$ and T. Bauer$^*$ and
T. Heumann$^*$ and E. Giannakouri$^*$ and D. Lipka$^*$ and
S. Jaeger and M. Schlesner$^*$ and P. Aloy and R. Eils$^*$
and C. Plass$^*$ and H. G. Augustin$^*$},
title = {{T}he transcriptomic and epigenetic map of vascular
quiescence in the continuous lung endothelium.},
journal = {eLife},
volume = {7},
issn = {2050-084X},
address = {Cambridge},
publisher = {eLife Sciences Publications},
reportid = {DKFZ-2018-00630},
pages = {e34423},
year = {2018},
note = {DKFZ-ZMBH-Allianz Plass C*, Augustin HG*, (*= Contributed
equally)},
abstract = {Maintenance of a quiescent and
organotypically-differentiated layer of blood vessel-lining
endothelial cells (EC) is vital for human health. Yet, the
molecular mechanisms of vascular quiescence remain largely
elusive. Here we identify the genome-wide transcriptomic
program controlling the acquisition of quiescence by
comparing lung EC of infant and adult mice, revealing a
prominent regulation of TGFß family members. These
transcriptomic changes are distinctly accompanied by
epigenetic modifications, measured at single CpG resolution.
Gain of DNA methylation affects developmental pathways,
including NOTCH signaling. Conversely, loss of DNA
methylation preferentially occurs in intragenic clusters
affecting intronic enhancer regions of genes involved in
TGFβ family signaling. Functional experiments
prototypically validated the strongly epigenetically
regulated inhibitors of TGFβ family signaling SMAD6 and
SMAD7 as regulators of EC quiescence. These data establish
the transcriptional and epigenetic landscape of vascular
quiescence that will serve as a foundation for further
mechanistic studies of vascular homeostasis and
disease-associated activation.},
cin = {A190 / C010 / B080 / B240 / L101},
ddc = {500},
cid = {I:(DE-He78)A190-20160331 / I:(DE-He78)C010-20160331 /
I:(DE-He78)B080-20160331 / I:(DE-He78)B240-20160331 /
I:(DE-He78)L101-20160331},
pnm = {321 - Basic Concepts (POF3-321)},
pid = {G:(DE-HGF)POF3-321},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29749927},
pmc = {pmc:PMC5947988},
doi = {10.7554/eLife.34423},
url = {https://inrepo02.dkfz.de/record/134840},
}