Hematopoietic stem cell and Ace2 regulation (PRJCA041153)
The emergence of hematopoietic stem and progenitor cells (HSPCs) during embryogenesis is a finely tuned process reliant on a delicate balance of inflammatory cues. While prior studies have identified pro-inflammatory pathways essential for HSPC development, how endothelial cells regulate and restrain inflammation to protect the hematopoietic niche remains largely unknown. Here, we uncover a conserved and endothelial-intrinsic role for Angiotensin-converting enzyme 2 (ACE2) in safeguarding embryonic hematopoiesis. Using zebrafish and mouse models, we show that ACE2 suppresses Nlrp3 Caspase-1-dependent pyroptosis. These findings uncover a previously unrecognized developmental role of ACE2 in maintaining hematopoietic niche integrity and highlight inflammation control as essential for early blood stem cell formation.