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Blood, 15 March 2002, Vol. 99, No. 6, pp. 2037-2044
HEMATOPOIESIS
Gene expression profiling identifies significant differences
between the molecular phenotypes of bone marrow-derived and
circulating human CD34+ hematopoietic stem cells
Ulrich Steidl,
Ralf Kronenwett,
Ulrich-Peter Rohr,
Roland Fenk,
Slawomir Kliszewski,
Christian Maercker,
Peter Neubert,
Manuel Aivado,
Judith Koch,
Olga Modlich,
Hans Bojar,
Norbert Gattermann, and
Rainer Haas
From the Department of Hematology, Oncology and
Clinical Immunology, University of Düsseldorf; German Resource
Center for Genome Research, Berlin; German Cancer Research Center,
Heidelberg; and Department of Chemical Oncology, University of
Düsseldorf, Germany.
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.
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