Searching for hematopoietic stem cells. II. The heterogeneity of Thy-1.1(lo)Lin(-/lo)Sca-1+ mouse hematopoietic stem cells separated by counterflow centrifugal elutriation

Exp Hematol. 1996 Apr;24(5):649-59.

Abstract

Mouse hematopoietic stem cells (HSCs) are highly enriched in the rare (approximately 0.05%) Thy-1.1(lo)Lin(-/lo)Sca-1+ fraction of hematopoietic tissues. It has been demonstrated that Thy-1.1(lo)Lin(-/lo)Sca-1+ cells are the only HSCs in C57BL/Ka-Thy-1.1 bone marrow. In this study, we separated C57/Ka-Thy-1.1 bone marrow cells by counterflow centrifugal elutriation (CCE) into four fractions and characterized Thy-1.1(lo)Lin(-/lo)Sca-1+ cells in each eluted fraction. The peak number of Thy-1.1(lo)Lin(-/lo)Sca-1+ cells was highly enriched in one eluted fraction, which was also highly enriched for day-12 to -13 CFU-S. Activities for day-13 CFU-S, radioprotection, and long-term multilineage reconstitution correlated with, and could be generally predicted by determining, the frequency of Thy-1.1(lo)Lin(-/lo)Sca-1+ cells in a given eluted fraction. However, the fraction that was highly enriched for blast cells and contained a low frequency of Thy-1.1(lo)Lin(-/lo)Sca-1+ cells, only provided short-term but not long-term radioprotection, with a predicted cell number (100 cells) that should have protected > or = 95% (PD95) of hosts. Still, when 300 Thy-1.1(lo)Lin(-/lo)Sca-1+ cells from this fraction (3 X PD95 for unfractionated HSCs) were injected, mice were radioprotected and donor cells provided long-term multilineage reconstitution. We propose that such blast cells may contain two Thy-1.1(lo)Lin(-/lo)Sca-1+ subsets, one providing short-term and the other long-term multilineage sustained hematopoiesis, the latter presumably due to HSC self-renewal.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Ly / analysis*
  • Antigens, Surface / analysis
  • Bone Marrow Cells
  • Cell Cycle
  • Cell Separation / methods*
  • Centrifugation
  • Cytapheresis / methods*
  • Female
  • Hematopoietic Stem Cells / cytology*
  • Immunophenotyping
  • Male
  • Membrane Proteins / analysis*
  • Mice
  • Mice, Inbred C57BL
  • Radiation Chimera
  • Thy-1 Antigens / analysis*

Substances

  • Antigens, Ly
  • Antigens, Surface
  • Ly6a protein, mouse
  • Membrane Proteins
  • Thy-1 Antigens