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Elife. 2015 Mar 30;4:e05521. doi: 10.7554/eLife.05521.

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

Author information

1
Department of Pediatrics and Children's Research Institute, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, United States.

Abstract

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.

KEYWORDS:

Angiopoietin-1; developmental biology; hematopoietic; mouse; niche; regeneration; stem cell; stem cells; vascular

PMID:
25821987
PMCID:
PMC4411515
DOI:
10.7554/eLife.05521
[Indexed for MEDLINE]
Free PMC Article

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