Primary human CD34⁺ hematopoietic stem and progenitor cells express functionally active receptors of neuromediators

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 [CRH1] and CRH2 receptors, orexin/hypocretin 1 and 2 receptors, GABA B receptor, adenosine A₂B receptor, opioid κ1 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 CD38^dim than in the CD38^bright 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.