Myc and its target Odc1 were among the most 250 strongly upregulated genes in Dll4 mutant ECs, compared with Notch1 and Rbpj mutants. Myc is known to activate important ribosome biogenesis and protein translation pathways, favoring cell growth. Dll4iDEC livers showed upregulation of a large range of canonical E2F, Myc, and mTORC1 target genes and ribosomal genes, particularly in the activated, proliferating, and endothelial tip-cell clusters. This hypermetabolic transcriptional status was confirmed by in-depth proteomics analysis of protein lysates obtained from freshly isolated liver ECs, providing the first proteomics analysis of the endothelial tip-cell state induced by targeting Dll4.