FIGURE 14.

Signaling and transcriptional networks regulating endothelial cell lineages. A: heterogeneity of pulmonary endothelial cells. Mesoderm-derived bipotential hemangioblasts differentiate into hematopoietic and endothelial progenitor cells (angioblasts). Angioblasts give a rise to arterial, venal, lymphatic, and capillary endothelial cell lineages. Arterial endothelial cell fate is promoted by NOTCH activation. Chicken ovalbumin in upstream promoter transcription factor 2 (COUP-TFII) inhibits NOTCH, enhances venous endothelial differentiation, and cooperates with PROX1, FOXC1/2, and SOX18 to stimulate lymphatic endothelial differentiation. Development of pulmonary capillary (microvascular) endothelial cells is promoted by FOXF1, SOX17, and NOTCH. B: transcriptional network regulating pulmonary endothelial development. Predicted endothelial cell regulatory gene network consists of representative transcription factors (green), signaling molecules (orange), and target genes (yellow). The regulatory relationships between key regulators and their predicted targets are identified through literature mining using the Ingenuity knowledge base. Solid lines indicate direct regulations. Dashed lines indicate indirect regulation.