title: Molecular evidence for stem cell function of the slow-dividing fraction among human hematopoietic progenitor cells by genome-wide analysis.
abstract: The molecular mechanisms that regulate asymmetric divisions of hematopoietic progenitor cells (HPCs) are not yet understood. The slow-dividing fraction (SDF) of HPCs is associated with primitive function and self-renewal, whereas the fast-dividing fraction (FDF) predominantly proceeds to differentiation. CD34+/CD38- cells of human umbilical cord blood were separated into the SDF and FDF. Genomewide 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 the 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.
authors.affiliation: Department of Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wagner
authors.forename: Alexandra
authors.initials: A
authors.lastname: Ansorge
authors.forename: Ute
authors.initials: U
authors.lastname: Wirkner
authors.forename: Volker
authors.initials: V
authors.lastname: Eckstein
authors.forename: Christian
authors.initials: C
authors.lastname: Schwager
authors.forename: Jonathon
authors.initials: J
authors.lastname: Blake
authors.forename: Katrin
authors.initials: K
authors.lastname: Miesala
authors.forename: Jan
authors.initials: J
authors.lastname: Selig
authors.forename: Rainer
authors.initials: R
authors.lastname: Saffrich
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Ansorge
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Ho
mesh_terms: D036541:ADP-ribosyl Cyclase / Q000097:blood; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD / Q000097:blood; D018952:Antigens, CD34 / Q000097:blood; D001483:Base Sequence; D002455:Cell Division / Q000235:genetics*; D017931:DNA Primers; D005312:Fetal Blood / Q000166:cytology; D020869:Gene Expression Profiling / Q000379:methods; D015894:Genome, Human; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007231:Infant, Newborn; D008562:Membrane Glycoproteins; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology*
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D017931:DNA Primers; D008562:Membrane Glycoproteins; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1