Further characterization of CD34-low/negative mouse hematopoietic stem cells

Ann N Y Acad Sci. 1999 Apr 30:872:57-66; discussion 66-70. doi: 10.1111/j.1749-6632.1999.tb08453.x.

Abstract

We have previously reported that in adult mouse bone marrow, CD34low/- c-kit+ Sca-1+ lineage markers negative (Lin-) (CD34-KSL) cells represent hematopoietic stem cells with long-term marrow repopulating ability whereas CD34+ c-kit+ Sca-1+ Lin- (CD34+KSL) cells are progenitors with short-term reconstitution capacity. To further characterize cells in those two populations, relative expression of various genes were examined by reverse transcriptase polymerase chain reaction (RT-PCR). In CD34-KSL cells, none of the genes studied was found to be expressed with the exception of GATA-2, IL-1R alpha, IL-2R gamma, AIC-2B, c-kit, EPO-R, and c-mpl. In contrast, expression of GATA-1 and all cytokine receptor genes examined except IL-2R beta, IL-7R alpha and IL-9R alpha were found in CD34+KSL. The difference between these two populations was also shown in single cell culture analysis of these cells. When cells were clone-sorted and cultured in the presence of SCF, IL-3 and EPO, CD34-KSL cells required much more time to undergo the first cell division than CD34+KSL cells. Dormancy and random fashion of cell division by CD34-KSL cells were also evident by the analysis of the second cell division, which was found to be delayed and unsynchronous compared with CD34+KSL cells. Clonal culture analysis showed that CD34-KSL cells were more potent in proliferation and multilineage differentiation capacities than CD34+KSL cells. In a paired-daughter cell experiment, 75% of CD34-KSL and 50% of CD34+KSL paired-daughter-derived colonies were nonidentical with wide variety of lineage combinations. Taken together, these data support our previous notion that CD34-KSL cells are at higher rank in hematopoietic hierarchy than CD34+KSL cells. In addition, our results using highly enriched stem cell population directly obtained from mouse bone marrow support the proposed stochastic nature of lineage commitment.

MeSH terms

  • Animals
  • Antigens, CD34 / analysis*
  • Biomarkers / analysis
  • Bone Marrow Cells / cytology*
  • Bone Marrow Cells / immunology
  • Cell Separation
  • DNA-Binding Proteins / genetics
  • GATA2 Transcription Factor
  • Gene Expression Regulation / immunology
  • Graft Survival
  • Hematopoietic Stem Cell Transplantation*
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / immunology
  • Mice
  • Radiation Protection
  • Receptors, Cytokine / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / genetics
  • Whole-Body Irradiation

Substances

  • Antigens, CD34
  • Biomarkers
  • DNA-Binding Proteins
  • GATA2 Transcription Factor
  • Gata2 protein, mouse
  • Receptors, Cytokine
  • Transcription Factors