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Blood, 1 August 2004, Vol. 104, No. 3, pp. 675-686.
Prepublished online as a Blood First Edition Paper on April 13, 2004; DOI 10.1182/blood-2003-10-3423.
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Submitted October 7, 2003
Accepted March 24, 2004
Molecular evidence for stem cell function of the slow dividing fraction among human hematopoietic progenitor cells by genome wide analysis
Wolfgang Wagner, Alexandra Ansorge, Ute Wirkner, Volker Eckstein, Christian Schwager, Jonathon Blake, Katrin Miesala, Jan Selig, Rainer Saffrich, Wilhelm Ansorge, and Anthony D Ho*
Medizinische Klinik und Poliklinik V, University of Heidelberg, Heidelberg, Germany
Functional Genomics Analysis, Biochemical Instrumentation Programme, European Molecular Biology Laboratory, Heidelberg, Germany
* Corresponding author; email: anthony_dick.ho{at}urz.uni-heidelberg.de.
The molecular mechanisms that regulate asymmetric divisions of hematopoietic progenitor cells (HPC) are not yet understood. The slow dividing fraction (SDF) of HPC is associated with primitive function and self-renewal while the fast dividing fraction (FDF) predominantly proceeds to differentiation. CD34+/CD38- cells of human umbilical cord blood were separated into SDF and FDF. Genome wide gene expression analysis of these populations was determined using the newly developed Human Transcriptome Microarray containing 51.145 cDNA clones of the Unigene Set-RZPD3. In addition, gene expression profiles of CD34+/CD38- cells were compared with those of CD34+/CD38+ cells. Among the genes showing the highest expression levels in the SDF were the following: CD133, erg, cyclin g2, MDR1, osteopontin, clqr1, ifi16, jak3, fzd6 and hoxa9, a pattern compatible with their primitive function and self-renewal capacity. Furthermore morphologic differences between SDF and FDF were determined. Cells in the SDF have more membrane protrusions and CD133 is located on these lamellipodia. The majority of cells in the SDF are rhodamine-123dull. These results provide molecular evidence that the SDF is associated with primitive function and serves as basis for a detailed understanding of asymmetric division of stem cells.

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