title: Role of neuropeptide Y in the bone marrow hematopoietic stem cell microenvironment.
abstract: The sympathetic nervous system (SNS) or neurotransmitters in the bone marrow microenvironment has been known to regulate hematopoietic stem cell (HSC) functions such as self-renewal, proliferation and differentiation. However, the specific role of neuropeptide Y (NPY) in this process remains relatively unexplored. In this study, we demonstrated that NPY deficient mice have significantly reduced HSC numbers and impaired bone marrow regeneration due to apoptotic destruction of SNS fibers and/or endothelial cells. Moreover, NPY treatment prevented bone marrow impairments in a mouse model of chemotherapy-induced SNS injury, while conditional knockout mice lacking the Y1 receptor in macrophages did not restore bone marrow dysfunction in spite of NPY injection. Transforming growth factor-beta (TGF-β) secreted by NPY-mediated Y1 receptor stimulation in macrophages plays a key role in neuroprotection and HSC survival in the bone marrow. Therefore, this study reveals a new role of NPY in bone marrow HSC microenvironment, and provides an insight into the therapeutic application of this neuropeptide.
authors.affiliation: Stem Cell Neuroplasticity Research Group, Kyungpook National University; Department of Physiology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University; Department of Biomedical Science, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University, Korea.
authors.forename: Min Hee
authors.initials: MH
authors.lastname: Park
authors.affiliation: Department of Orthopaedic Surgery, Kyungpook National University Hospital, Daegu 41944, Korea.
authors.forename: Woo-Kie
authors.initials: WK
authors.lastname: Min
authors.affiliation: Stem Cell Neuroplasticity Research Group, Kyungpook National University; Department of Laboratory Animal Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Korea.
authors.forename: Hee Kyung
authors.initials: HK
authors.lastname: Jin
authors.affiliation: Stem Cell Neuroplasticity Research Group, Kyungpook National University; Department of Physiology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University; Department of Biomedical Science, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University, Korea.
authors.forename: Jae-Sung
authors.initials: JS
authors.lastname: Bae
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009478:Neuropeptide Y / Q000172:deficiency / Q000378:metabolism*; D017476:Receptors, Neuropeptide Y / Q000378:metabolism; D055153:Stem Cell Niche
chemical_list: D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor