TY - JOUR TI - The transcriptomic and epigenetic map of vascular quiescence in the continuous lung endothelium AU - Schlereth, Katharina AU - Weichenhan, Dieter AU - Bauer, Tobias AU - Heumann, Tina AU - Giannakouri, Evangelia AU - Lipka, Daniel AU - Jaeger, Samira AU - Schlesner, Matthias AU - Aloy, Patrick AU - Eils, Roland AU - Plass, Christoph AU - Augustin, Hellmut G A2 - Stainier, Didier YR VL - 7 PY - 2018 DA - 2018/05/11 SP - e34423 C1 - eLife 2018;7:e34423 DO - 10.7554/eLife.34423 UR - https://doi.org/10.7554/eLife.34423 AB - 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. KW - endothelial quiescence KW - endothelial trsanscriptome KW - endothelial epigenome KW - DNA methylation KW - TGFß JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -