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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.
HEMATOPOIESIS Primary human CD34+ hematopoietic stem and progenitor cells express functionally active receptors of neuromediatorsFrom the Department of Hematology, Oncology and Clinical Immunology, Heinrich Heine University, Duesseldorf, Germany; Harvard Institutes of Medicine, Boston, MA; the Department of Neurophysiology, Heinrich Heine University, Duesseldorf, Germany; the Department of Endocrinology, Heinrich Heine University, Duesseldorf, Germany; and the German Resource Center for Genome Research, Berlin/Heidelberg, Germany.
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 reverse-transcriptase–polymerase chain reaction (RT-PCR), and fluorescent-activated cell sorter (FACS) analysis focusing on genes involved in neurobiologic 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 (corticotropin-releasing hormone 1 [CRH 1] and CRH 2 receptors, orexin/hypocretin 1 and 2 receptors, GABAB receptor, adenosine A2B receptor, opioid
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| Copyright © 2004 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
1 and µ1 receptors, and 5-HT 1F receptor). As shown by 2-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 cyclic adenosine monophosphate (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. 
