title: Primary human CD34+ hematopoietic stem and progenitor cells express functionally active receptors of neuromediators.
abstract: 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.
authors.affiliation: Department of Hematology, Oncology and Clinical Immunology, Heinrich Heine University, Duesseldorf, Germany. usteidl@bidmc.harvard.edu
authors.forename: Ulrich
authors.initials: U
authors.lastname: Steidl
authors.forename: Simone
authors.initials: S
authors.lastname: Bork
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schaub
authors.forename: Oliver
authors.initials: O
authors.lastname: Selbach
authors.forename: Janette
authors.initials: J
authors.lastname: Seres
authors.forename: Manuel
authors.initials: M
authors.lastname: Aivado
authors.forename: Thomas
authors.initials: T
authors.lastname: Schroeder
authors.forename: Ulrich-Peter
authors.initials: UP
authors.lastname: Rohr
authors.forename: Roland
authors.initials: R
authors.lastname: Fenk
authors.forename: Slawomir
authors.initials: S
authors.lastname: Kliszewski
authors.forename: Christian
authors.initials: C
authors.lastname: Maercker
authors.forename: Peter
authors.initials: P
authors.lastname: Neubert
authors.forename: Stefan R
authors.initials: SR
authors.lastname: Bornstein
authors.forename: Helmut L
authors.initials: HL
authors.lastname: Haas
authors.forename: Guido
authors.initials: G
authors.lastname: Kobbe
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Tenen
authors.forename: Rainer
authors.initials: R
authors.lastname: Haas
authors.forename: Ralf
authors.initials: R
authors.lastname: Kronenwett
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement; D003598:Cytoskeletal Proteins / Q000096:biosynthesis; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism; D049030:Dystroglycans; D005110:Extracellular Space / Q000378:metabolism; D020869:Gene Expression Profiling; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D007473:Ion Channels / Q000096:biosynthesis / Q000235:genetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008565:Membrane Proteins / Q000096:biosynthesis; D009414:Nerve Growth Factors / Q000096:biosynthesis; D020411:Oligonucleotide Array Sequence Analysis; D050683:R-SNARE Proteins; D012333:RNA, Messenger / Q000096:biosynthesis; D017981:Receptors, Neurotransmitter / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D018952:Antigens, CD34; D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D007473:Ion Channels; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009414:Nerve Growth Factors; D050683:R-SNARE Proteins; D012333:RNA, Messenger; D017981:Receptors, Neurotransmitter; D049030:Dystroglycans