Safeguarding lymphatic identity: cooperative Erg and Fli1 activity in lymphatic vascular homeostasis

Although transcriptional programs driving lymphatic endothelial cell (LEC) specification are being increasingly characterized, far less is known about the postnatal mechanisms that preserve lymphatic vessel identity and function. In this issue of the JCI, Yang et al. show that the E26 transformation-specific (ETS) transcription factors ETS-related gene (Erg) and Friend leukemia integration 1 (Fli1) cooperatively maintain adult LEC homeostasis by sustaining transcriptionally distinct LEC populations, vascular integrity, immune-vascular interactions, and repression of proinflammatory and prothrombotic gene programs. These findings extend the known roles of Erg and Fli1 beyond the blood endothelium and provide mechanistic insight into human lymphatic disease associated with Erg haploinsufficiency.