National Institute of Biological Sciences, Beijing, China.
Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, China.
Nat Cell Biol. 2023 Dec;25(12):1746-1757. doi: 10.1038/s41556-023-01284-9. Epub 2023 Nov 27.
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.
骨髓中含有外周神经，可促进辐射或化疗（骨髓清除）后的造血再生，但人们对其如何受到调节知之甚少。在这里，我们发现瘦素受体表达（LepR）基质细胞产生的神经生长因子（NGF）对于维持成年骨髓中的神经纤维是必需的。在无神经的骨髓中，稳态造血正常，但骨髓清除后造血和血管再生受损。LepR 细胞及其衍生的脂肪细胞在骨髓清除后增加了 NGF 的产生，促进了骨髓中的神经发芽以及造血和血管再生。神经通过激活 LepR 细胞中的β2 和β3 肾上腺素能受体信号转导，以及潜在的脂肪细胞，促进多种造血和血管再生生长因子的产生，从而促进再生。外周神经和 LepR 细胞通过一种互惠关系促进骨髓再生，其中 LepR 细胞通过合成 NGF 来维持神经，而神经通过促进 LepR 细胞产生生长因子来增加再生。
