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dc.contributor.authorFielding, Claire
dc.contributor.authorGarcía-García, Andrés
dc.contributor.authorKorn, Claudia
dc.contributor.authorGadomski, Stephen
dc.contributor.authorFang, Zijian
dc.contributor.authorReguera, Juan L
dc.contributor.authorPérez-Simón, José A
dc.contributor.authorGottgens, Berthold
dc.contributor.authorMéndez-Ferrer, Simón
dc.date.accessioned2022-01-14T00:31:29Z
dc.date.available2022-01-14T00:31:29Z
dc.date.issued2022-01-27
dc.identifier.issn2041-1723
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/332704
dc.description.abstractThe 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.
dc.publisherNature Research
dc.rightsAll Rights Reserved
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserved
dc.subjectCambridge Stem Cell Institute
dc.titleCholinergic signals preserve haematopoietic stem cell quiescence during regenerative haematopoiesis.
dc.typeArticle
dc.publisher.departmentDepartment of Haematology
dc.date.updated2022-01-13T11:18:16Z
prism.publicationNameNat Commun
dc.identifier.doi10.17863/CAM.80148
dcterms.dateAccepted2022-01-12
rioxxterms.versionofrecord10.1038/s41467-022-28175-1
rioxxterms.versionAM
dc.contributor.orcidGarcía-García, Andrés [0000-0002-8797-649X]
dc.contributor.orcidPérez-Simón, José A [0000-0003-3616-6101]
dc.contributor.orcidGottgens, Berthold [0000-0001-6302-5705]
dc.contributor.orcidMéndez-Ferrer, Simón [0000-0002-9805-9988]
dc.identifier.eissn2041-1723
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (203151/Z/16/Z)
pubs.funder-project-idWellcome Trust (203151/A/16/Z)
pubs.funder-project-idEuropean Research Council (648765)
pubs.funder-project-idMRC (MR/V005421/1)
pubs.funder-project-idCancer Research UK (C61367/A26670)
cam.orpheus.successTue Feb 01 19:02:44 GMT 2022 - Embargo updated
cam.depositDate2022-01-13
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement
rioxxterms.freetoread.startdate2022-07-27


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