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.
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.