Endothelial PERK restricts lymphoid regeneration by reducing DLL4-NOTCH3 signaling at the Pre-B niche.
- Open access
Ablating endothelial PERK enhances DLL4-NOTCH3 signaling, boosting lymphoid regeneration by 50% after irradiation in hematopoietic recovery.
- Why it matters: Delayed immune recovery after stem cell transplants worsens patient outcomes, yet the mechanisms controlling lymphoid regeneration in the bone marrow microenvironment are not fully understood.
- What they did: The study used mouse models and single-cell analysis to show that removing endothelial Perk increases DLL4 expression, which activates NOTCH3 in mesenchymal stromal cells, promoting lymphoid progenitor expansion.
- The result: Blocking PERK improves immune recovery by enhancing DLL4-NOTCH3 signaling, suggesting that targeting ER stress pathways could be a promising approach to accelerate hematopoietic regeneration post-transplant.