학술논문

Leptin receptor+cells promote bone marrow innervation and regeneration by synthesizing nerve growth factor
Document Type
Article
Source
Nature Cell Biology; 20230101, Issue: Preprints p1-12, 12p
Subject
Language
ISSN
14657392; 14764679
Abstract
The bone marrow contains peripheral nerves that promote haematopoietic regeneration after irradiation or chemotherapy (myeloablation), but little is known about how this is regulated. Here we found that nerve growth factor (NGF) produced by leptin receptor-expressing (LepR+) stromal cells is required to maintain nerve fibres in adult bone marrow. In nerveless bone marrow, steady-state haematopoiesis was normal but haematopoietic and vascular regeneration were impaired after myeloablation. LepR+cells, and the adipocytes they gave rise to, increased NGF production after myeloablation, promoting nerve sprouting in the bone marrow and haematopoietic and vascular regeneration. Nerves promoted regeneration by activating β2 and β3 adrenergic receptor signalling in LepR+cells, and potentially in adipocytes, increasing their production of multiple haematopoietic and vascular regeneration growth factors. Peripheral nerves and LepR+cells thus promote bone marrow regeneration through a reciprocal relationship in which LepR+cells sustain nerves by synthesizing NGF and nerves increase regeneration by promoting the production of growth factors by LepR+cells.