title: Signals from the sympathetic nervous system regulate hematopoietic stem cell egress from bone marrow.
abstract: Hematopoietic stem and progenitor cells (HSPC), attracted by the chemokine CXCL12, reside in specific niches in the bone marrow (BM). HSPC migration out of the BM is a critical process that underlies modern clinical stem cell transplantation. Here we demonstrate that enforced HSPC egress from BM niches depends critically on the nervous system. UDP-galactose ceramide galactosyltransferase-deficient (Cgt(-/-)) mice exhibit aberrant nerve conduction and display virtually no HSPC egress from BM following granulocyte colony-stimulating factor (G-CSF) or fucoidan administration. Adrenergic tone, osteoblast function, and bone CXCL12 are dysregulated in Cgt(-/-) mice. Pharmacological or genetic ablation of adrenergic neurotransmission indicates that norepinephrine (NE) signaling controls G-CSF-induced osteoblast suppression, bone CXCL12 downregulation, and HSPC mobilization. Further, administration of a beta(2) adrenergic agonist enhances mobilization in both control and NE-deficient mice. Thus, these results indicate that the sympathetic nervous system regulates the attraction of stem cells to their niche.
authors.affiliation: Department of Medicine, Immunobiology Center and Black Family Stem Cell Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Katayama
authors.forename: Michela
authors.initials: M
authors.lastname: Battista
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Kao
authors.forename: Andrés
authors.initials: A
authors.lastname: Hidalgo
authors.forename: Anna J
authors.initials: AJ
authors.lastname: Peired
authors.forename: Steven A
authors.initials: SA
authors.lastname: Thomas
authors.forename: Paul S
authors.initials: PS
authors.lastname: Frenette
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001854:Bone Marrow Cells / Q000187:drug effects*; D002465:Cell Movement; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism; D015536:Down-Regulation; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D011828:Radiation Chimera; D013564:Sympathetic Nervous System / Q000502:physiology*
chemical_list: D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D016179:Granulocyte Colony-Stimulating Factor