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Open Access Green as soon as Postprint is submitted to ZB.
Primary human CD34+ hematopoietic stem and progenitor cells express functionally active receptors of neuromediators.
Blood 104, 81-88 (2004)
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 A(2)B receptor, opioid kappa 1 and mu 1 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.
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Publication type
Article: Journal article
Document type
Scientific Article
Language
english
Publication Year
2004
HGF-reported in Year
0
ISSN (print) / ISBN
0006-4971
e-ISSN
1528-0020
Journal
Blood
Quellenangaben
Volume: 104,
Issue: 1,
Pages: 81-88
Publisher
American Society of Hematology
Reviewing status
Peer reviewed
Institute(s)
Institute of Pancreatic Islet Research (IPI)
PubMed ID
15016651
Erfassungsdatum
2004-12-31