Quantification of self-renewal capacity in single hematopoietic stem cells from normal and Lnk-deficient mice

Dev Cell. 2005 Jun;8(6):907-14. doi: 10.1016/j.devcel.2005.03.019.

Abstract

Despite being a hallmark of hematopoietic stem cells (HSCs), HSC self-renewal has never been quantitatively assessed. Establishment of a clonal and quantitative assay for HSC function permitted demonstration that adult mouse HSCs are significantly heterogeneous in degree of multilineage repopulation and that higher repopulating potential reflects higher self-renewal activity. An HSC with high repopulating potential could regenerate approximately 1000 HSCs, whereas the repopulating activity of regenerated HSCs on average was significantly reduced, indicating extensive but limited self-renewal capacity in HSCs. Comparisons of wild-type mice with mutant mice deficient in the signal adaptor molecule Lnk showed that not only HSC numbers but also the self-renewal capacity of some HSCs are markedly increased when Lnk function is lost. Lnk appears to control HSC numbers by negatively regulating HSC self-renewal signaling.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Antigens, CD34 / genetics
  • Bone Marrow Cells / physiology
  • Bone Marrow Transplantation
  • Cell Count
  • Cell Differentiation*
  • Cell Proliferation
  • Cells, Cultured / drug effects
  • Cells, Cultured / transplantation
  • Clone Cells / drug effects
  • Clone Cells / transplantation
  • Coculture Techniques / methods
  • Flow Cytometry / methods
  • Hematopoiesis*
  • Hematopoietic Stem Cell Transplantation*
  • Hematopoietic Stem Cells / physiology*
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Mice
  • Mice, Knockout
  • Proteins / genetics*
  • RNA, Messenger / biosynthesis
  • Radiation Chimera
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Statistics, Nonparametric

Substances

  • Antigens, CD34
  • Intracellular Signaling Peptides and Proteins
  • Lnk protein, mouse
  • Membrane Proteins
  • Proteins
  • RNA, Messenger