The transcriptomic and epigenetic map of vascular quiescence in the continuous lung endothelium

ELife
Katharina SchlerethHellmut G Augustin

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.

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Citations

Jul 5, 2019·International Journal of Molecular Sciences·Vera van de PolMarie-José Goumans
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Datasets Mentioned

BETA
GSE86600
GSE87374

Methods Mentioned

BETA
RNA-seq
FACS
WGBS
PCR
methylation profiling
ELISA
dissection
FCS
Flow
Assay

Software Mentioned

Reactome
Galaxy
bsseq
: Profiler
STAR
Ingenuity Pathway Analysis
IGV browser
MassARRAY
Gene Set Enrichment Analysis ( GSEA )
Fiji

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