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

被引:119
作者
Steidl, U
Kronenwett, R
Rohr, UP
Fenk, R
Kliszewski, S
Maercker, C
Neubert, P
Aivado, M
Koch, J
Modlich, O
Bojar, H
Gatterman, N
Haas, R
机构
[1] Univ Dusseldorf, Klin Hamatol Onkol & Klin Immunol, Dept Hematol Oncol & Clin Immunol, D-40225 Dusseldorf, Germany
[2] German Resource Ctr Genome Res, Berlin, Germany
[3] German Canc Res Ctr, D-6900 Heidelberg, Germany
[4] Univ Dusseldorf, Dept Chem Oncol, D-4000 Dusseldorf, Germany
关键词
D O I
10.1182/blood.V99.6.2037
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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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页码:2037 / 2044
页数:8
相关论文
共 48 条
[1]   BEHAVIOR OF HEMATOPOIETIC STEM-CELLS IN A LARGE ANIMAL [J].
ABKOWITZ, JL ;
PERSIK, MT ;
SHELTON, GH ;
OTT, RL ;
KIKLEVICH, JV ;
CATLIN, SN ;
GUTTORP, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (06) :2031-2035
[2]   Cell differentiation - Hepatocytes from nonhepatic adult stem cells [J].
Alison, MR ;
Poulsom, R ;
Jeffery, R ;
Dhillon, AP ;
Quaglia, A ;
Jacob, J ;
Novelli, M ;
Prentice, G ;
Williamson, J ;
Wright, NA .
NATURE, 2000, 406 (6793) :257-257
[3]  
Beissbarth T, 2000, BIOINFORMATICS, V16, P1014
[4]   ECTOPIC EXPRESSION OF A CONDITIONAL GATA-2 ESTROGEN-RECEPTOR CHIMERA ARRESTS ERYTHROID-DIFFERENTIATION IN A HORMONE-DEPENDENT MANNER [J].
BRIEGEL, K ;
LIM, KC ;
PLANK, C ;
BEUG, H ;
ENGEL, JD ;
ZENKE, M .
GENES & DEVELOPMENT, 1993, 7 (06) :1097-1109
[5]   The role of MCM/P1 proteins in the licensing of DNA replication [J].
Chong, JPJ ;
Thommes, P ;
Blow, JJ .
TRENDS IN BIOCHEMICAL SCIENCES, 1996, 21 (03) :102-106
[6]  
CROSS NCP, 1994, LEUKEMIA, V8, P186
[7]   Homing-associated cell adhesion molecule (H-CAM/CD44) on human CD34+ hematopoietic progenitor cells [J].
Deguchi, T ;
Komada, Y .
LEUKEMIA & LYMPHOMA, 2000, 40 (1-2) :25-+
[8]   Expression of the human immunodeficiency virus type-1 coreceptors CXCR-4 (fusin, LESTR) and CKR-5 in CD34(+) hematopoietic progenitor cells [J].
Deichmann, M ;
Kronenwett, R ;
Haas, R .
BLOOD, 1997, 89 (10) :3522-3528
[9]   Proteinase-activated receptors:: novel mechanisms of signaling by serine proteases [J].
Déry, O ;
Corvera, CU ;
Steinhoff, M ;
Bunnett, NW .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 1998, 274 (06) :C1429-C1452
[10]  
DUHRSEN U, 1988, BLOOD, V72, P2074