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 [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.
Steidl
Ulrich
U
Department of Hematology, Oncology and Clinical Immunology, Heinrich Heine University, Duesseldorf, Germany. usteidl@bidmc.harvard.edu
Bork
Simone
S
Schaub
Sebastian
S
Selbach
Oliver
O
Seres
Janette
J
Aivado
Manuel
M
Schroeder
Thomas
T
Rohr
Ulrich-Peter
UP
Fenk
Roland
R
Kliszewski
Slawomir
S
Maercker
Christian
C
Neubert
Peter
P
Bornstein
Stefan R
SR
Haas
Helmut L
HL
Kobbe
Guido
G
Tenen
Daniel G
DG
Haas
Rainer
R
Kronenwett
Ralf
R
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
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