Gene expression profiling identifies significant differences between the molecular phenotypes of bone marrow-derived and circulating human CD34+ hematopoietic stem cells.
CD34+ hematopoietic stem cells are used clinically to support cytotoxic therapy, and recent studies raised hope that they could even serve as a cellular source for nonhematopoietic tissue engineering. Here, we examined in 18 volunteers the gene expressions of 1185 genes in highly enriched bone marrow CD34+ (BM-CD34+) or granulocyte-colony-stimulating factor-mobilized peripheral blood CD34+ (PB-CD34+) cells by means of cDNA array technology to identify molecular causes underlying the functional differences between circulating and sedentary hematopoietic stem and progenitor cells. In total, 65 genes were significantly differentially expressed. Greater cell cycle and DNA synthesis activity of BM-CD34+ than PB-CD34+ cells were reflected by the 2- to 5-fold higher expression of 9 genes involved in cell cycle progression, 11 genes regulating DNA synthesis, and cell cycle-initiating transcription factor E2F-1. Conversely, 9 other transcription factors, including the differentiation blocking GATA2 and N-myc, were expressed 2 to 3 times higher in PB-CD34+ cells than in BM-CD34+ cells. Expression of 5 apoptosis driving genes was also 2 to 3 times greater in PB-CD34+ cells, reflecting a higher apoptotic activity. In summary, our study provides a gene expression profile of primary human CD34+ hematopoietic cells of the blood and marrow. Our data molecularly confirm and explain the finding that CD34+ cells residing in the bone marrow cycle more rapidly, whereas circulating CD34+ cells consist of a higher number of quiescent stem and progenitor cells. Moreover, our data provide novel molecular insight into stem cell physiology.
Steidl
Ulrich
U
Department of Hematology, Oncology and Clinical Immunology, University of Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf, Germany. usteidl@usteidl.de
Kronenwett
Ralf
R
Rohr
Ulrich-Peter
UP
Fenk
Roland
R
Kliszewski
Slawomir
S
Maercker
Christian
C
Neubert
Peter
P
Aivado
Manuel
M
Koch
Judith
J
Modlich
Olga
O
Bojar
Hans
H
Gattermann
Norbert
N
Haas
Rainer
R
D018952:Antigens, CD34 / Q000097:blood*; D017209:Apoptosis / Q000235:genetics; D001773:Blood Cells / Q000378:metabolism / Q000502:physiology; D001854:Bone Marrow Cells / Q000378:metabolism / Q000502:physiology; D018797:Cell Cycle Proteins; D016000:Cluster Analysis; D004261:DNA Replication / Q000235:genetics; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D020869:Gene Expression Profiling; D018816:Genes, cdc; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D010641:Phenotype; D014157:Transcription Factors / Q000235:genetics
D018952:Antigens, CD34; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D014157:Transcription Factors