title: Hematopoietic stem and progenitor cells regulate the regeneration of their niche by secreting Angiopoietin-1.
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.
authors.affiliation: Department of Pediatrics and Children's Research Institute, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Bo O
authors.initials: BO
authors.lastname: Zhou
authors.affiliation: Department of Pediatrics and Children's Research Institute, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Lei
authors.initials: L
authors.lastname: Ding
authors.affiliation: Department of Pediatrics and Children's Research Institute, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Morrison
mesh_terms: D042683:Angiopoietin-1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001808:Blood Vessels / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D002199:Capillary Permeability / Q000528:radiation effects; D005260:Female; D005720:Gamma Rays; D005786:Gene Expression Regulation; D006410:Hematopoiesis / Q000235:genetics / Q000528:radiation effects; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D008297:Male; D008533:Megakaryocytes / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D051379:Mice; D008822:Mice, Transgenic; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000235:genetics* / Q000528:radiation effects; D015398:Signal Transduction; D055153:Stem Cell Niche / Q000235:genetics* / Q000528:radiation effects; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects
chemical_list: D042683:Angiopoietin-1; C467628:Angpt1 protein, mouse; C577485:Nes protein, mouse; D064231:Nestin; D054411:Receptors, Leptin; C515447:leptin receptor, mouse; D019009:Proto-Oncogene Proteins c-kit; C045073:Cre recombinase; D019426:Integrases
keywords: Angiopoietin-1; developmental biology; hematopoietic; mouse; niche; regeneration; stem cell; stem cells; vascular
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