Balancing act: how Apelin tunes vascular and haemogenic identities

Haematopoietic stem and progenitor cells (HSPCs) maintain haematopoiesis throughout life. Their formation occurs early in embryonic development and is regulated by many intrinsic and extrinsic factors that delicately balance the need to maintain a vascular network with the need to generate HSPCs de novo. Most extrinsic factors such as BMP and Notch act instructively in haemogenic endothelial cells to induce HSPC fates. A new study by Eberlein et al (2025) identifies a key role for Apelin signalling acting indirectly by limiting the number of arterial endothelial cells that become haemogenic, independently of Notch, BMP or Wnt signalling (Eberlein et al, 2025). Arterial endothelial cells that do not respond to Apelin more frequently convert to the haemogenic endothelial cell fate, giving rise to higher numbers of haematopoietic stem and progenitor cells in the embryo that persist into adulthood. This work highlights a critical temporal window where Apelin functions as a rheostat, balancing angiogenesis, vascular maintenance and haematopoiesis.