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Stem Cells 2005;23:496-506 www.StemCells.com
© 2005 AlphaMed Press

The Kinetic Status of Hematopoietic Stem Cell Subpopulations Underlies a Differential Expression of Genes Involved in Self-Renewal, Commitment, and Engraftment

Rossella Manfredinia, Roberta Zinia, Simona Salatia, Michela Sienaa, Elena Tenedinia, Enrico Tagliaficoa, Monica Montanaria, Tommaso Zanocco-Marania, Claudia Gemellia, Tatiana Vignudellia, Alexis Grandea, Miriam Foglib, Lara Rossib, Maria Elena Fagiolib, Lucia Catanib, Roberto M. Lemolib, Sergio Ferraria

a Department of Biological Sciences, Biochemistry Section, University of Modena and Reggio Emilia, Modena, Italy;
b Institute of Hematology and Medical Oncology "L. & A. Seragnoli," University of Bologna, Italy

Key Words. CD34+ stem cells • CD34 • Hematopoietic stem cells • Microarray • Proliferation • Self-renewal • Differentiation • Engraftment

Correspondence: Sergio Ferrari, M.D., Dipartimento di Scienze Biomediche, Sezione di Chimica Biologica, Università di Modena e Reggio Emilia, Via Campi 287, 41100 Modena, Italy. Telephone: 39-059-2055400; Fax: 39-059-2055410; e-mail: ferrari.sergio{at}unimo.it

The gene expression profile of CD34 hematopoietic stem cells (HSCs) and the correlations with their biological properties are still poorly understood. To address this issue, we used the DNA microarray technology to compare the expression profiles of different peripheral blood hemopoietic stem/progenitor cell subsets, lineage-negative (Lin) CD34, LinCD34+, and Lin+CD34+ cells. The analysis of gene categories differentially expressed shows that the expression of CD34 is associated with cell cycle entry and metabolic activation, such as DNA, RNA, and protein synthesis. Moreover, the significant upregulation in CD34 cells of pathways inhibiting HSC proliferation induces a strong differential expression of cyclins, cyclin-dependent kinases (CDKs), CDK inhibitors, and growth-arrest genes. According to the expression of their receptors and transducers, interleukin (IL)-10 and IL-17 showed an inhibitory effect on the clonogenic activity of CD34 cells. Conversely, CD34+ cells were sensitive to the mitogenic stimulus of thrombopoietin. Furthermore, CD34 cells express preferentially genes related to neural, epithelial, and muscle differentiation. The analysis of transcription factor expression shows that the CD34 induction results in the upregulation of genes related to self-renewal and lineage commitment. The preferential expression in CD34+ cells of genes supporting the HSC mobilization and homing to the bone marrow, such as chemokine receptors and integrins, gives the molecular basis for the higher engraftment capacity of CD34+ cells. Thus, the different kinetic status of CD34 and CD34+ cells, detailed by molecular and functional analysis, significantly influences their biological behavior.




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