Cholinergic signals preserve haematopoietic stem cell quiescence during regenerative haematopoiesis
| Autor: | Fielding, Claire, García-García, Andrés, Korn, Claudia, Gadomski, Stephen, Fang, Zijian, Reguera, Juan L, Pérez-Simón, José A, Gottgens, Berthold, Méndez-Ferrer, Simón |
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| Přispěvatelé: | National Institutes of Health (US), International Scholarship at The University of Cambridge, European Commission, European Research Council, MRC Cambridge Stem Cell Institute, National Health Institute Blood and Transplant (UK), Cancer Research UK, Wellcome Trust, García-García, Andrés [0000-0002-8797-649X], Pérez-Simón, José A [0000-0003-3616-6101], Göttgens, Berthold [0000-0001-6302-5705], Méndez-Ferrer, Simón [0000-0002-9805-9988], Apollo - University of Cambridge Repository, Universidad de Sevilla. Departamento de Medicina, Gottgens, Berthold [0000-0001-6302-5705] |
| Rok vydání: | 2022 |
| Předmět: |
Glial Cell Line-Derived Neurotrophic Factor Receptors
Science Cholinergic Agents General Physics and Astronomy 13/106 Haematopoietic stem General Biochemistry Genetics and Molecular Biology 631/532/2139 13/1 Mice 13/100 Bone Marrow Risk Factors 631/443/63 Animals Humans 14/19 Bone 49/91 631/532/2118/1542 Multidisciplinary Cambridge Stem Cell Institute Haematopoietic stem cells article Hematopoietic Stem Cell Transplantation Mesenchymal Stem Cells General Chemistry Hematopoietic Stem Cells Chemokine CXCL12 Hematopoiesis 13/31 Cholinergic signals Receptors Adrenergic beta-3 13/51 14/63 692/499 Stem-cell niche Regenerative haematopoiesis |
| Zdroj: | Nature Communications, Vol 13, Iss 1, Pp 1-13 (2022) Digital.CSIC. Repositorio Institucional del CSIC instname Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-022-28175-1 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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