Nature (London), 2021-01, Vol.589 (7843), p.591-596
2021
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- Autor(en) / Beteiligte
- Titel
- Nociceptive nerves regulate haematopoietic stem cell mobilization
- Ist Teil von
- Nature (London), 2021-01, Vol.589 (7843), p.591-596
- Ort / Verlag
- London: Nature Publishing Group UK
- Erscheinungsjahr
- 2021
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Haematopoietic stem cells (HSCs) reside in specialized microenvironments in the bone marrow—often referred to as ‘niches’—that represent complex regulatory milieux influenced by multiple cellular constituents, including nerves 1 , 2 . Although sympathetic nerves are known to regulate the HSC niche 3 – 6 , the contribution of nociceptive neurons in the bone marrow remains unclear. Here we show that nociceptive nerves are required for enforced HSC mobilization and that they collaborate with sympathetic nerves to maintain HSCs in the bone marrow. Nociceptor neurons drive granulocyte colony-stimulating factor (G-CSF)-induced HSC mobilization via the secretion of calcitonin gene-related peptide (CGRP). Unlike sympathetic nerves, which regulate HSCs indirectly via the niche 3 , 4 , 6 , CGRP acts directly on HSCs via receptor activity modifying protein 1 (RAMP1) and the calcitonin receptor-like receptor (CALCRL) to promote egress by activating the Gα s /adenylyl cyclase/cAMP pathway. The ingestion of food containing capsaicin—a natural component of chili peppers that can trigger the activation of nociceptive neurons—significantly enhanced HSC mobilization in mice. Targeting the nociceptive nervous system could therefore represent a strategy to improve the yield of HSCs for stem cell-based therapeutic agents. Stimulation of pain-sensing neurons, which can be achieved in mice by the ingestion of capsaicin, promotes the migration of haematopoietic stem cells from the bone marrow into the blood.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0028-0836eISSN: 1476-4687DOI: 10.1038/s41586-020-03057-yTitel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7856173
- Format
- –
- Schlagworte
- 13, 13/1, 13/100, 13/31, 13/51, 38, 38/39, 42, 631/378/1959/2605, 631/532/1542, 64, 64/60, 692/308/2171, Adenylate cyclase, Adenylyl Cyclases - metabolism, Animals, Autonomic Pathways - drug effects, Bone marrow, Calcitonin, Calcitonin gene-related peptide, Calcitonin Gene-Related Peptide - metabolism, Calcitonin Receptor-Like Protein - metabolism, Capsaicin, Capsaicin - pharmacology, Cell Movement - drug effects, Cerebrospinal fluid, Chemical compounds, Collaboration, Colony-stimulating factor, Control, Cyclic AMP - metabolism, Egress, Female, Granulocyte colony-stimulating factor, Granulocyte Colony-Stimulating Factor - metabolism, GTP-Binding Protein alpha Subunits, Gs - metabolism, Hematopoietic stem cells, Hematopoietic Stem Cells - cytology, Hematopoietic Stem Cells - drug effects, Hematopoietic Stem Cells - metabolism, Humanities and Social Sciences, Ingestion, Leukocytes (granulocytic), Male, Methods, Mice, Mice, Inbred C57BL, Microenvironments, multidisciplinary, Nerves, Nervous system, Neurons, Neuropeptides, Neurotransmitters, Nociception - drug effects, Nociception - physiology, Nociceptors, Nociceptors - drug effects, Nociceptors - physiology, Pain perception, Peppers, Pharmacology, Physiological aspects, Receptor activity modifying proteins, Receptor Activity-Modifying Protein 1 - metabolism, Receptors, Regulation, Science, Science (multidisciplinary), Sensory stimulation, Signal Transduction - drug effects, Stem Cell Niche, Stem cell transplantation, Stem cells, Sympathetic nerves, Sympathetic Nervous System - cytology, Sympathetic Nervous System - drug effects