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Neuropeptide Y regulates the hematopoietic stem cell microenvironment and prevents nerve injury in the bone marrow |
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| Authors: | Woo‐Kie Min Won Woo Lee Jeong Eun Lee Haruhiko Akiyama Herbert Herzog Grigori N Enikolopov Edward H Schuchman Jae‐sung Bae |
| Affiliation: | 1. Department of Orthopaedic Surgery, Kyungpook National University Hospital, Daegu, Korea;2. Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Korea;3. Department of Radiation Oncology, Kyungpook National University Hospital, Daegu, Korea;4. Department of Orthopaedics, Kyoto University, Kyoto, Japan;5. Neuroscience Research Program, Garvan Institute of Medical Research, Sydney, NSW, Australia;6. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, NY, USA;7. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA;8. Stem Cell Neuroplasticity Research Group, Kyungpook National University, Daegu, Korea;9. Department of Physiology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea;10. Department of Biomedical Science, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University, Daegu, Korea |
| Abstract: | Many reports have revealed the importance of the sympathetic nervous system (SNS) in the control of the bone marrow environment. However, the specific role of neuropeptide Y (NPY) in this process has not been systematically studied. Here we show that NPY‐deficient mice have significantly reduced hematopoietic stem cell (HSC) numbers and impaired regeneration in bone marrow due to apoptotic destruction of SNS fibers and/or endothelial cells. Furthermore, pharmacological elevation of NPY prevented bone marrow impairments in a mouse model of chemotherapy‐induced SNS injury, while NPY injection into conditional knockout mice lacking the Y1 receptor in macrophages did not relieve bone marrow dysfunction. These results indicate that NPY promotes neuroprotection and restores bone marrow dysfunction from chemotherapy‐induced SNS injury through the Y1 receptor in macrophages. They also reveal a new role of NPY as a regulator of the bone marrow microenvironment and highlight the potential therapeutic value of this neuropeptide. |
| Keywords: | bone marrow microenvironment hematopoietic stem cell neuropeptide Y regeneration sympathetic nervous system |