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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.

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