Hematopoietic stem and progenitor cells regulate the regeneration of their niche by secreting Angiopoietin-1

Hematopoietic stem cells (HSCs) are maintained by a perivascular niche in bone marrow but it is unclear whether the niche is reciprocally regulated by HSCs. Here, we systematically assessed the expression and function of Angiopoietin-1 (Angpt1) in bone marrow. Angpt1 was not expressed by osteoblasts. Angpt1 was most highly expressed by HSCs, and at lower levels by c-kit(+) hematopoietic progenitors, megakaryocytes, and Leptin Receptor(+) (LepR(+)) stromal cells. Global conditional deletion of Angpt1, or deletion from osteoblasts, LepR(+) cells, Nes-cre-expressing cells, megakaryocytes, endothelial cells or hematopoietic cells in normal mice did not affect hematopoiesis, HSC maintenance, or HSC quiescence. Deletion of Angpt1 from hematopoietic cells and LepR(+) cells had little effect on vasculature or HSC frequency under steady-state conditions but accelerated vascular and hematopoietic recovery after irradiation while increasing vascular leakiness. Hematopoietic stem/progenitor cells and LepR(+) stromal cells regulate niche regeneration by secreting Angpt1, reducing vascular leakiness but slowing niche recovery.