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Publication : Meteorin links the bone marrow hypoxic state to hematopoietic stem/progenitor cell mobilization.

First Author  Dai YW Year  2022
Journal  Cell Rep Volume  40
Issue  12 Pages  111361
PubMed ID  36130501 Mgi Jnum  J:347509
Mgi Id  MGI:7343471 Doi  10.1016/j.celrep.2022.111361
Citation  Dai YW, et al. (2022) Meteorin links the bone marrow hypoxic state to hematopoietic stem/progenitor cell mobilization. Cell Rep 40(12):111361
abstractText  Hematopoietic stem/progenitor cells (HSPCs) are supported and regulated by niche cells in the bone marrow with an important characterization of physiological hypoxia. However, how hypoxia regulates HSPCs is still unclear. Here, we find that meteorin (Metrn) from hypoxic macrophages restrains HSPC mobilization. Hypoxia-induced factor 1alpha and Yin Yang 1 induce the high expression of Metrn in macrophages, and macrophage-specific Metrn knockout increases HSPC mobilization through modulating HSPC proliferation and migration. Mechanistically, Metrn interacts with its receptor 5-hydroxytryptamine receptor 2b (Htr2b) to regulate the reactive oxygen species levels in HSPCs through targeting phospholipase C signaling. The reactive oxygen species levels are reduced in HSPCs of macrophage-specific Metrn knockout mice with activated phospholipase C signaling. Targeting the Metrn/Htr2b axis could therefore be a potential strategy to improve HSPC mobilization for stem cell-based therapy.
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