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Leptin Receptor+ cells promote bone marrow innervationandregeneration by synthesizing nerve growth factor

摘要:The bone marrow contains peripheral nerves that promote hematopoietic regeneration after irradiation or chemotherapy(myeloablation) but little is known about how this is regulated. We found that nerve growth factor (NGF) produced by LeptinReceptor-expressing (LepR+) stromal cells is required to maintain nerve fibers in adult bone marrow. In nerveless bone marrow, steady-state hematopoiesis was normal but hematopoietic and vascular regeneration were impaired after myeloablation. LepR+ cells, and the adipocytes they gave rise to, increased NGF production after myeloablation, promoting nerve sproutingin the bone marrow and hematopoietic and vascular regeneration. Nerves promoted regeneration by activating b2 and b3adrenergic receptor signaling in LepR+ cells, and potentially in adipocytes, increasing their production of multiplehematopoietic and vascular regeneration growth factors. Peripheral nerves and LepR+ cells thus promote bone marrowregeneration through a reciprocal relationship in which LepR+ cells sustain nerves by synthesizing NGF and nerves increaseregeneration by promoting the production of growth factors by LepR+ cells.

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