干细胞
造血
生物
胆碱能的
细胞生物学
骨髓
造血干细胞
成体干细胞
免疫学
癌症研究
内皮干细胞
神经科学
遗传学
体外
作者
Claire Fielding,Andrés García‐García,Claudia Korn,Stephen Gadomski,Zijian Fang,Juan Luís Reguera,José Antonio Pérez-Simón,Berthold Göttgens,Simón Méndez-Ferrer
标识
DOI:10.1038/s41467-022-28175-1
摘要
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.
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