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

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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.

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Bo O Zhou

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

Competing interests
No competing interests declared.
Lei Ding

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

Competing interests
No competing interests declared.
Sean J Morrison

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

For correspondence
sean.morrison@utsouthwestern.edu

Competing interests
Sean J Morrison, Senior editor, eLife.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All mice were housed at the Unit for Laboratory Animal Medicine at the University of Michigan or in the Animal Resource Center at the University of Texas Southwestern Medical Center. All protocols were approved by the University of Michigan Committee on the Use and Care Animals and by the University of Texas Southwestern Institutional Animal Care and Use Committee (protocol 2011-0104).

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