Signals from the sympathetic nervous system regulate hematopoietic stem cell egress from bone marrow |
| |
Authors: | Katayama Yoshio Battista Michela Kao Wei-Ming Hidalgo Andrés Peired Anna J Thomas Steven A Frenette Paul S |
| |
Institution: | Department of Medicine, Immunobiology Center and Black Family Stem Cell Institute, Mount Sinai School of Medicine, New York, NY 10029, USA. |
| |
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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|