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

Yoshio Katayama; Michela Battista; Wei Ming Kao; Andrés Hidalgo; Anna J. Peired; Steven A. Thomas; Paul S. Frenette

doi:10.1016/j.cell.2005.10.041

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

Yoshio Katayama, Michela Battista, Wei Ming Kao, Andrés Hidalgo, Anna J. Peired, Steven A. Thomas, Paul S. Frenette

Research output: Contribution to journal › Article › peer-review

1115 Scopus citations

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 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.

Original language	English
Pages (from-to)	407-421
Number of pages	15
Journal	Cell
Volume	124
Issue number	2
DOIs	https://doi.org/10.1016/j.cell.2005.10.041
State	Published - 27 Jan 2006

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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 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.",

author = "Yoshio Katayama and Michela Battista and Kao, {Wei Ming} and Andr{\'e}s Hidalgo and Peired, {Anna J.} and Thomas, {Steven A.} and Frenette, {Paul S.}",

note = "Funding Information: We are very grateful to Dr. Brian Popko for providing breeding pairs of Cgt mice. We thank Drs. Raymond Johnson for NE measurements, Etsuko Abe for the gift of osteoblast lines (MC3T3-E1 and UMSA-33), Lynda F. Bonewald for the MLO-Y4 cell line, and William G.M. Janssen and John H. Morrison for giving us access to a stereotaxic apparatus and Sumitomo Pharmaceuticals (Osaka, Japan) for L-DOPS. We also thank Goutham Narla for excellent advice about Q-PCR and Dr. Sergio Lira for helpful animated discussions. This work was supported by the National Institutes of Health grants DK56638 and HL69438, National Blood Foundation Fellowship (A.H.), and an NIH training grant T32 DK07792 (W.-M. K.). ",

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T1 - Signals from the sympathetic nervous system regulate hematopoietic stem cell egress from bone marrow

AU - Katayama, Yoshio

AU - Battista, Michela

AU - Kao, Wei Ming

AU - Hidalgo, Andrés

AU - Peired, Anna J.

AU - Thomas, Steven A.

AU - Frenette, Paul S.

N1 - Funding Information: We are very grateful to Dr. Brian Popko for providing breeding pairs of Cgt mice. We thank Drs. Raymond Johnson for NE measurements, Etsuko Abe for the gift of osteoblast lines (MC3T3-E1 and UMSA-33), Lynda F. Bonewald for the MLO-Y4 cell line, and William G.M. Janssen and John H. Morrison for giving us access to a stereotaxic apparatus and Sumitomo Pharmaceuticals (Osaka, Japan) for L-DOPS. We also thank Goutham Narla for excellent advice about Q-PCR and Dr. Sergio Lira for helpful animated discussions. This work was supported by the National Institutes of Health grants DK56638 and HL69438, National Blood Foundation Fellowship (A.H.), and an NIH training grant T32 DK07792 (W.-M. K.).

PY - 2006/1/27

Y1 - 2006/1/27

N2 - 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.

AB - 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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Signals from the sympathetic nervous system regulate hematopoietic stem cell egress from bone marrow

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