Gene expression profiling identifies significant differences between the molecular phenotypes of bone marrow-derived and circulating human CD34+ hematopoietic stem cells

Ulrich G. Steidl, Ralf Kronenwett, Ulrich Peter Rohr, Roland Fenk, Slawomir Kliszewski, Christian Maercker, Peter Neubert, Manuel Aivado, Judith Koch, Olga Modlich, Hans Bojar, Norbert Gattermann, Rainer Haas

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

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 cycleinitiating 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.

Original languageEnglish (US)
Pages (from-to)2037-2044
Number of pages8
JournalBlood
Volume99
Issue number6
DOIs
StatePublished - Mar 15 2002
Externally publishedYes

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Gene Expression Profiling
Hematopoietic Stem Cells
Stem cells
Gene expression
Blood Cells
Bone
Blood
Genes
Bone Marrow
Phenotype
Stem Cells
Cells
Cell Cycle
E2F1 Transcription Factor
Gene Expression
Cell Physiological Phenomena
DNA
Physiology
Granulocyte Colony-Stimulating Factor
Tissue Engineering

ASJC Scopus subject areas

  • Hematology

Cite this

Gene expression profiling identifies significant differences between the molecular phenotypes of bone marrow-derived and circulating human CD34+ hematopoietic stem cells. / Steidl, Ulrich G.; Kronenwett, Ralf; Rohr, Ulrich Peter; Fenk, Roland; Kliszewski, Slawomir; Maercker, Christian; Neubert, Peter; Aivado, Manuel; Koch, Judith; Modlich, Olga; Bojar, Hans; Gattermann, Norbert; Haas, Rainer.

In: Blood, Vol. 99, No. 6, 15.03.2002, p. 2037-2044.

Research output: Contribution to journalArticle

Steidl, UG, Kronenwett, R, Rohr, UP, Fenk, R, Kliszewski, S, Maercker, C, Neubert, P, Aivado, M, Koch, J, Modlich, O, Bojar, H, Gattermann, N & Haas, R 2002, 'Gene expression profiling identifies significant differences between the molecular phenotypes of bone marrow-derived and circulating human CD34+ hematopoietic stem cells', Blood, vol. 99, no. 6, pp. 2037-2044. https://doi.org/10.1182/blood.V99.6.2037
Steidl, Ulrich G. ; Kronenwett, Ralf ; Rohr, Ulrich Peter ; Fenk, Roland ; Kliszewski, Slawomir ; Maercker, Christian ; Neubert, Peter ; Aivado, Manuel ; Koch, Judith ; Modlich, Olga ; Bojar, Hans ; Gattermann, Norbert ; Haas, Rainer. / Gene expression profiling identifies significant differences between the molecular phenotypes of bone marrow-derived and circulating human CD34+ hematopoietic stem cells. In: Blood. 2002 ; Vol. 99, No. 6. pp. 2037-2044.
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AU - Fenk, Roland

AU - Kliszewski, Slawomir

AU - Maercker, Christian

AU - Neubert, Peter

AU - Aivado, Manuel

AU - Koch, Judith

AU - Modlich, Olga

AU - Bojar, Hans

AU - Gattermann, Norbert

AU - Haas, Rainer

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N2 - 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 cycleinitiating 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.

AB - 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 cycleinitiating 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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