Cholinergic signals preserve haematopoietic stem cell quiescence during regenerative haematopoiesis.
Reguera, Juan L
MetadataShow full item record
Fielding, C., García-García, A., Korn, C., Gadomski, S., Fang, Z., Reguera, J. L., Pérez-Simón, J. A., et al. (2022). Cholinergic signals preserve haematopoietic stem cell quiescence during regenerative haematopoiesis.. Nat Commun https://doi.org/10.1038/s41467-022-28175-1
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.
Cambridge Stem Cell Institute
Wellcome Trust (203151/Z/16/Z)
Wellcome Trust (203151/A/16/Z)
European Research Council (648765)
Cancer Research UK (C61367/A26670)
Embargo Lift Date
External DOI: https://doi.org/10.1038/s41467-022-28175-1
This record's URL: https://www.repository.cam.ac.uk/handle/1810/332704
All Rights Reserved
Licence URL: http://www.rioxx.net/licenses/all-rights-reserved