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Cholinergic signals preserve haematopoietic stem cell quiescence during regenerative haematopoiesis
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Cholinergic signals preserve haematopoietic stem cell quiescence during regenerative haematopoiesis
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Cholinergic signals preserve haematopoietic stem cell quiescence during regenerative haematopoiesis
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Journal Article
Cholinergic signals preserve haematopoietic stem cell quiescence during regenerative haematopoiesis
2022
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/100
/ 13/106
/ 13/31
/ 13/51
/ 14/19
/ 14/63
/ 49/91
/ 692/499
/ Animals
/ Chemokine CXCL12 - metabolism
/ Cholinergic Agents - metabolism
/ Glial Cell Line-Derived Neurotrophic Factor Receptors - genetics
/ Hematopoietic Stem Cell Transplantation
/ Hematopoietic Stem Cells - metabolism
/ Humanities and Social Sciences
/ Humans
/ Mesenchymal Stem Cells - metabolism
/ Mice
/ Nicotine
/ Receptors, Adrenergic, beta-3 - metabolism
/ Science
