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Blood, 1 July 2004, Vol. 104, No. 1, pp. 81-88.
Prepublished online as a Blood First Edition Paper on March 11, 2004; DOI 10.1182/blood-2004-01-0373.


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Submitted January 29, 2004
Accepted February 28, 2004

Primary Human CD34+ Hematopoietic Stem and Progenitor Cells Express Functionally Active Receptors of Neuromediators

Ulrich Steidl*, Simone Bork, Sebastian Schaub, Oliver Selbach, Janette Seres, Manuel Aivado, Thomas Schroeder, Ulrich P Rohr, Roland Fenk, Slawomir Kliszewski, Christian Maercker, Peter Neubert, Stefan R Bornstein, Helmut L Haas, Guido Kobbe, Daniel G Tenen, Rainer Haas, and Ralf Kronenwett

Dept. of Hematology, Oncology, and Clinical Immunology, Heinrich Heine University Duesseldorf, Duesseldorf, Germany; Harvard Institutes of Medicine, Boston, MA, USA
Dept. of Hematology, Oncology, and Clinical Immunology, Heinrich Heine University Duesseldorf, Duesseldorf, Germany
Dept. of Neurophysiology, Heinrich Heine University Duesseldorf, Duesseldorf, Germany
Dept. of Endocrinology, Heinrich Heine University Duesseldorf, Duesseldorf, Germany
Harvard Institutes of Medicine, Boston, MA, USA
German Resource Center for Genome Research, Berlin/Heidelberg, Germany

* Corresponding author; email: usteidl{at}bidmc.harvard.edu.

Recently, overlapping molecular phenotypes of hematopoietic and neuropoietic cells were described in mice. Here, we examined primary human CD34+ hematopoietic stem and progenitor cells applying specialized cDNA arrays, real-time RT-PCR, and FACS analysis focusing on genes involved in neurobiological functions. We found expression of vesicle fusion and motility genes, ligand- and voltage-gated ion channels, receptor kinases and phosphatases, and most interestingly, mRNA as well as protein expression of G protein-coupled receptors of neuromediators (CRH 1 and 2 receptors, orexin/hypocretin 1 and 2 receptors, GABA B receptor, adenosine A2B receptor, opioid {kappa}1 and µ1 receptors, 5-HT 1F receptor). As shown by two-color immunofluorescence the protein expression of these receptors was higher in the more immature CD38dim than in the CD38bright subset within the CD34+ population, and completely absent in fully differentiated blood cells, suggesting that those receptors play a role in developmentally early CD34+ stem and progenitor cells. The intracellular concentration of cAMP in CD34+ cells was diminished significantly upon stimulation of either CRH or orexin receptors indicating that those are functionally active and coupled to inhibitory G proteins in human hematopoietic cells. In conclusion, these findings suggest a molecular interrelation of neuronal and hematopoietic signaling mechanisms in humans.


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