Cholinergic signals preserve haematopoietic stem cell quiescence during regenerative haematopoiesis.
Cholinergic signals preserve haematopoietic stem cell quiescence during regenerative haematopoiesis.
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DOI：
10.1038/s41467-022-28175-1
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发表时间：
2022-01-27
影响因子：
16.6
通讯作者：
Méndez-Ferrer S
中科院分区：
文献类型：
--
作者：
Fielding C;García-García A;Korn C;Gadomski S;Fang Z;Reguera JL;Pérez-Simón JA;Göttgens B;Méndez-Ferrer S
交感神经系统已被进化选择来响应压力，并通过去甲肾上腺素能信号激活造血干细胞。然而，在增殖应激下维持造血干细胞静止和维持的途径在很大程度上仍然未知。在这里，我们发现胆碱能信号保持造血干细胞在骨相关（骨内膜）骨髓龛的静止。骨髓胆碱能神经信号在应激造血过程中增加，并通过胆碱能骨祖细胞放大。缺乏胆碱能神经支配会损害对化疗或放疗的平衡反应，并减少造血干细胞的静止和自我更新。胆碱能信号激活骨髓间充质基质细胞中的α7烟碱受体，导致CXCL12表达增加和造血干细胞静止因此，尼古丁暴露增加体内骨内膜造血干细胞静止，并损害小鼠造血干细胞移植后的造血再生。在人类中，吸烟史与异基因造血干细胞移植后血小板计数恢复正常延迟相关。这些结果表明，胆碱能信号保持干细胞静止增殖压力。交感神经系统已被证明对压力作出反应并激活造血干细胞。在这里，他们表明，骨髓中的胆碱能信号保持造血干细胞在增殖应激下的静止和自我更新。
The sympathetic nervous system has been evolutionary selected to respond to stress and activates haematopoietic stem cells via noradrenergic signals. However, the pathways preserving haematopoietic stem cell quiescence and maintenance under proliferative stress remain largely unknown. Here we found that cholinergic signals preserve haematopoietic stem cell quiescence in bone-associated (endosteal) bone marrow niches. Bone marrow cholinergic neural signals increase during stress haematopoiesis and are amplified through cholinergic osteoprogenitors. Lack of cholinergic innervation impairs balanced responses to chemotherapy or irradiation and reduces haematopoietic stem cell quiescence and self-renewal. Cholinergic signals activate α7 nicotinic receptor in bone marrow mesenchymal stromal cells leading to increased CXCL12 expression and haematopoietic stem cell quiescence. Consequently, nicotine exposure increases endosteal haematopoietic stem cell quiescence in vivo and impairs hematopoietic regeneration after haematopoietic stem cell transplantation in mice. In humans, smoking history is associated with delayed normalisation of platelet counts after allogeneic haematopoietic stem cell transplantation. These results suggest that cholinergic signals preserve stem cell quiescence under proliferative stress. The sympathetic nervous system has been shown to respond to stress and activate haematopoietic stem cells. Here they show that cholinergic signals in the bone marrow preserve haematopoietic stem cell quiescence and self-renewal under proliferative stress.
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影响因子：
7.7
作者：
Isern J;García-García A;Martín AM;Arranz L;Martín-Pérez D;Torroja C;Sánchez-Cabo F;Méndez-Ferrer S
通讯作者：
Méndez-Ferrer S
影响因子：
82.9
作者：
Guo B;Huang X;Lee MR;Lee SA;Broxmeyer HE
通讯作者：
Broxmeyer HE
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
3.7
作者：
Forsberg EC;Passegué E;Prohaska SS;Wagers AJ;Koeva M;Stuart JM;Weissman IL
通讯作者：
Weissman IL
影响因子：
20.3
作者：
Garcia-Garcia, Andres;Korn, Claudia;Mendez-Ferrer, Simon
通讯作者：
Mendez-Ferrer, Simon