Reduced Competitive Repopulation Capacity of Multipotential Hematopoietic Stem Cells in the Bone Marrow of Friend

Michael W Epperly1, Xichen Zhang1, Renee Fisher1

  • 1Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, U.S.A.

Abstract

Insights

Friend virus infection expands hematopoietic stem cells in susceptible mice but not resistant mice. Resistant mice show no expansion of stem or progenitor cells, indicating a protective genetic mechanism.

Area of Science:

  • Hematology
  • Virology
  • Immunogenetics

Background:

  • Friend leukemia virus (FVP) causes lethal erythroleukemia and splenomegaly in susceptible mice.
  • Genetic resistance (Fv-2r) in C57BL/6 mice confers protection against FVP-induced disease.
  • Investigating the hematopoietic stem cell (HSC) pool in resistant mice is crucial for understanding FVP pathogenesis.

Purpose of the Study:

  • To determine if the HSC pool expands in Fv-2r-resistant mice following FVP infection.
  • To compare HSC pool expansion in resistant (Fv-2r) versus susceptible (Fv-2s) mouse strains.
  • To elucidate the role of genetic resistance in regulating hematopoietic stem cell dynamics during viral infection.

Main Methods:

  • Competitive repopulation assay (120-day bone marrow transplantation) was employed.
  • Assessed HSC pool expansion in FVP-infected Fv-2r C57BL/6 mice.
  • Quantified committed hematopoietic progenitor cells in vitro.

Main Results:

  • Susceptible Fv-2s FVB mice showed significant expansion of committed hematopoietic progenitors after FVP infection.
  • Resistant Fv-2r C57BL/6 mice did not exhibit expansion of committed hematopoietic progenitors.
  • No detectable expansion of multipotential stem cells or committed progenitor cells was observed in Fv-2r mice via competitive repopulation.

Conclusions:

  • FVP disease in Fv-2s mice is linked to committed hematopoietic progenitor expansion.
  • Fv-2r mice demonstrate resistance, showing no expansion of progenitor or stem cell populations.
  • Genetic resistance (Fv-2r) prevents aberrant hematopoietic stem cell proliferation during Friend virus infection.

Related Concept Videos