Signals From the Sympathetic Nervous System Regulate Hematopoietic Stem Cell Egress From Bone Marrow

Cell. 2006 Jan 27;124(2):407-21. doi: 10.1016/j.cell.2005.10.041.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Bone Marrow Cells / drug effects*
  • Cell Movement*
  • Chemokine CXCL12
  • Chemokines, CXC / metabolism
  • Down-Regulation
  • Granulocyte Colony-Stimulating Factor / pharmacology*
  • Hematopoietic Stem Cells / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism*
  • Radiation Chimera
  • Sympathetic Nervous System / physiology*

Substances

  • Chemokine CXCL12
  • Chemokines, CXC
  • Cxcl12 protein, mouse
  • Granulocyte Colony-Stimulating Factor