Catecholaminergic neurotransmitters regulate migration and repopulation of immature human CD34+ cells through Wnt signaling

Asaf Spiegel; Shoham Shivtiel; Alexander Kalinkovich; Aya Ludin; Neta Netzer; Polina Goichberg; Yaara Azaria; Igor Resnick; Izhar Hardan; Herzel Ben-Hur; Arnon Nagler; Menachem Rubinstein; Tsvee Lapidot

doi:10.1038/ni1509

Catecholaminergic neurotransmitters regulate migration and repopulation of immature human CD34⁺ cells through Wnt signaling

Asaf Spiegel, Shoham Shivtiel, Alexander Kalinkovich, Aya Ludin, Neta Netzer, Polina Goichberg, Yaara Azaria, Igor Resnick, Izhar Hardan, Herzel Ben-Hur, Arnon Nagler, Menachem Rubinstein, Tsvee Lapidot^*

^*Corresponding author for this work

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

280 Scopus citations

Abstract

Catecholamines are important regulators of homeostasis, yet their functions in hematopoiesis are poorly understood. Here we report that immature human CD34⁺ cells dynamically expressed dopamine and β₂-adrenergic receptors, with higher expression in the primitive CD34⁺CD38^lo population. The myeloid cytokines G-CSF and GM-CSF upregulated neuronal receptor expression on immature CD34⁺ cells. Treatment with neurotransmitters increased the motility, proliferation and colony formation of human progenitor cells, correlating with increased polarity, expression of the metalloproteinase MT1-MMP and activity of the metalloproteinase MMP-2. Treatment with catecholamines enhanced human CD34⁺ cell engraftment of NOD-SCID mice through Wnt signaling activation and increased cell mobilization and bone marrow Sca-1⁺ c-Kit⁺Lin^- cell numbers. Our results identify new functions for neurotransmitters and myeloid cytokines in the direct regulation of human and mouse progenitor cell migration and development.

Original language	English
Pages (from-to)	1123-1131
Number of pages	9
Journal	Nature Immunology
Volume	8
Issue number	10
DOIs	https://doi.org/10.1038/ni1509
State	Published - Oct 2007
Externally published	Yes

Funding

Funders	Funder number
Helen and Martin Kimmel Institute for Stem Cell Research
Weizmann Institute of Science
Israel Science Foundation	796/04

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/ni1509

Cite this

Spiegel, A., Shivtiel, S., Kalinkovich, A., Ludin, A., Netzer, N., Goichberg, P., Azaria, Y., Resnick, I., Hardan, I., Ben-Hur, H., Nagler, A., Rubinstein, M., & Lapidot, T. (2007). Catecholaminergic neurotransmitters regulate migration and repopulation of immature human CD34⁺ cells through Wnt signaling. Nature Immunology, 8(10), 1123-1131. https://doi.org/10.1038/ni1509

@article{dc56dfbb27424b4ea2564d320985b36e,

title = "Catecholaminergic neurotransmitters regulate migration and repopulation of immature human CD34+ cells through Wnt signaling",

abstract = "Catecholamines are important regulators of homeostasis, yet their functions in hematopoiesis are poorly understood. Here we report that immature human CD34+ cells dynamically expressed dopamine and β2-adrenergic receptors, with higher expression in the primitive CD34+CD38lo population. The myeloid cytokines G-CSF and GM-CSF upregulated neuronal receptor expression on immature CD34+ cells. Treatment with neurotransmitters increased the motility, proliferation and colony formation of human progenitor cells, correlating with increased polarity, expression of the metalloproteinase MT1-MMP and activity of the metalloproteinase MMP-2. Treatment with catecholamines enhanced human CD34+ cell engraftment of NOD-SCID mice through Wnt signaling activation and increased cell mobilization and bone marrow Sca-1+ c-Kit+Lin- cell numbers. Our results identify new functions for neurotransmitters and myeloid cytokines in the direct regulation of human and mouse progenitor cell migration and development.",

author = "Asaf Spiegel and Shoham Shivtiel and Alexander Kalinkovich and Aya Ludin and Neta Netzer and Polina Goichberg and Yaara Azaria and Igor Resnick and Izhar Hardan and Herzel Ben-Hur and Arnon Nagler and Menachem Rubinstein and Tsvee Lapidot",

note = "Funding Information: We thank L. Abel for assistance; E. Tzahor (Weizmann Institute of Science) for CRD-Frzb-enriched conditioned medium; and A. Globerson and S. Berrih-Aknin for discussions and critical review of the manuscript. Supported by Ares-Serono, the Gabriella Rich Center for Transplantation Biology, the Israel Science Foundation (796/04) and the Helen and Martin Kimmel Institute for Stem Cell Research at the Weizmann Institute of Science.",

year = "2007",

month = oct,

doi = "10.1038/ni1509",

language = "אנגלית",

volume = "8",

pages = "1123--1131",

journal = "Nature Immunology",

issn = "1529-2908",

publisher = "Nature Publishing Group",

number = "10",

}

Spiegel, A, Shivtiel, S, Kalinkovich, A, Ludin, A, Netzer, N, Goichberg, P, Azaria, Y, Resnick, I, Hardan, I, Ben-Hur, H , Nagler, A, Rubinstein, M & Lapidot, T 2007, 'Catecholaminergic neurotransmitters regulate migration and repopulation of immature human CD34⁺ cells through Wnt signaling', Nature Immunology, vol. 8, no. 10, pp. 1123-1131. https://doi.org/10.1038/ni1509

TY - JOUR

T1 - Catecholaminergic neurotransmitters regulate migration and repopulation of immature human CD34+ cells through Wnt signaling

AU - Spiegel, Asaf

AU - Shivtiel, Shoham

AU - Kalinkovich, Alexander

AU - Ludin, Aya

AU - Netzer, Neta

AU - Goichberg, Polina

AU - Azaria, Yaara

AU - Resnick, Igor

AU - Hardan, Izhar

AU - Ben-Hur, Herzel

AU - Nagler, Arnon

AU - Rubinstein, Menachem

AU - Lapidot, Tsvee

N1 - Funding Information: We thank L. Abel for assistance; E. Tzahor (Weizmann Institute of Science) for CRD-Frzb-enriched conditioned medium; and A. Globerson and S. Berrih-Aknin for discussions and critical review of the manuscript. Supported by Ares-Serono, the Gabriella Rich Center for Transplantation Biology, the Israel Science Foundation (796/04) and the Helen and Martin Kimmel Institute for Stem Cell Research at the Weizmann Institute of Science.

PY - 2007/10

Y1 - 2007/10

N2 - Catecholamines are important regulators of homeostasis, yet their functions in hematopoiesis are poorly understood. Here we report that immature human CD34+ cells dynamically expressed dopamine and β2-adrenergic receptors, with higher expression in the primitive CD34+CD38lo population. The myeloid cytokines G-CSF and GM-CSF upregulated neuronal receptor expression on immature CD34+ cells. Treatment with neurotransmitters increased the motility, proliferation and colony formation of human progenitor cells, correlating with increased polarity, expression of the metalloproteinase MT1-MMP and activity of the metalloproteinase MMP-2. Treatment with catecholamines enhanced human CD34+ cell engraftment of NOD-SCID mice through Wnt signaling activation and increased cell mobilization and bone marrow Sca-1+ c-Kit+Lin- cell numbers. Our results identify new functions for neurotransmitters and myeloid cytokines in the direct regulation of human and mouse progenitor cell migration and development.

AB - Catecholamines are important regulators of homeostasis, yet their functions in hematopoiesis are poorly understood. Here we report that immature human CD34+ cells dynamically expressed dopamine and β2-adrenergic receptors, with higher expression in the primitive CD34+CD38lo population. The myeloid cytokines G-CSF and GM-CSF upregulated neuronal receptor expression on immature CD34+ cells. Treatment with neurotransmitters increased the motility, proliferation and colony formation of human progenitor cells, correlating with increased polarity, expression of the metalloproteinase MT1-MMP and activity of the metalloproteinase MMP-2. Treatment with catecholamines enhanced human CD34+ cell engraftment of NOD-SCID mice through Wnt signaling activation and increased cell mobilization and bone marrow Sca-1+ c-Kit+Lin- cell numbers. Our results identify new functions for neurotransmitters and myeloid cytokines in the direct regulation of human and mouse progenitor cell migration and development.

UR - http://www.scopus.com/inward/record.url?scp=34548777583&partnerID=8YFLogxK

U2 - 10.1038/ni1509

DO - 10.1038/ni1509

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

AN - SCOPUS:34548777583

SN - 1529-2908

VL - 8

SP - 1123

EP - 1131

JO - Nature Immunology

JF - Nature Immunology

IS - 10

ER -