RT Journal Article
T1 Cholinergic signals preserve haematopoietic stem cell quiescence during regenerative haematopoiesis.
A1 Fielding, Claire
A1 Garcia-Garcia, Andres
A1 Korn, Claudia
A1 Gadomski, Stephen
A1 Fang, Zijian
A1 Reguera, Juan L
A1 Perez-Simon, Jose A
A1 Göttgens, Berthold
A1 Mendez-Ferrer, Simon
K1 Animals
K1 Chemokine CXCL12
K1 Hematopoiesis
K1 Hematopoietic Stem Cells
K1 Mesenchymal Stem Cells
K1 Risk Factors
AB 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.
PB Nature Publishing Group
YR 2022
FD 2022-01-27
LK http://hdl.handle.net/10668/19537
UL http://hdl.handle.net/10668/19537
LA en
NO Fielding C, García-García A, Korn C, Gadomski S, Fang Z, Reguera JL, et al. Cholinergic signals preserve haematopoietic stem cell quiescence during regenerative haematopoiesis. Nat Commun. 2022 Jan 27;13(1):543.
DS RISalud
RD Apr 7, 2025