[HTML][HTML] Signals from the sympathetic nervous system regulate hematopoietic stem cell egress from bone marrow

Y Katayama, M Battista, WM Kao, A Hidalgo, AJ Peired… - Cell, 2006 - cell.com
Y Katayama, M Battista, WM Kao, A Hidalgo, AJ Peired, SA Thomas, PS Frenette
Cell, 2006cell.com
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 …
Summary
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 β2 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.
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