期刊
ELIFE
卷 4, 期 -, 页码 -出版社
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.05521
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资金
- National Heart, Lung, and Blood Institute (NHBLI) [HL097760]
- Howard Hughes Medical Institute (HHMI)
- Leukemia and Lymphoma Society (LLS) fellowship
- Helen Hay Whitney Foundation (HHWF)
- Howard Hughes Medical Institute (HHMI) Investigator
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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